1 00:00:01,000 --> 00:00:03,880 When this is all over and done with, 2 00:00:03,880 --> 00:00:06,120 I will literally be able to leap out of bed. 3 00:00:06,120 --> 00:00:07,440 That'll be fantastic. 4 00:00:10,800 --> 00:00:16,080 It's 2012 and 42 men and women are about to take part 5 00:00:16,080 --> 00:00:19,360 in one of the world's most ambitious medical trials... 6 00:00:19,360 --> 00:00:20,680 See you later. 7 00:00:21,960 --> 00:00:25,160 ..a search for a cure for Parkinson's. 8 00:00:25,160 --> 00:00:26,200 OK. 9 00:00:26,200 --> 00:00:29,200 We're asking people to have experimental brain surgery. 10 00:00:29,200 --> 00:00:31,480 So, we're going right posterior. Yeah. 11 00:00:31,480 --> 00:00:34,200 We're asking people to have an experimental device 12 00:00:34,200 --> 00:00:36,160 inserted into their heads. 13 00:00:36,160 --> 00:00:38,200 We're going to drive the needles in, OK? 14 00:00:38,200 --> 00:00:39,840 That's fine. 15 00:00:39,840 --> 00:00:42,600 We're asking people to have an experimental drug. 16 00:00:45,280 --> 00:00:50,000 We could do great harm here and we could genuinely make people 17 00:00:50,000 --> 00:00:52,720 worse than they are before they started. 18 00:00:52,720 --> 00:00:54,440 For the last six years, 19 00:00:54,440 --> 00:00:57,320 cameras have been given unprecedented access to film 20 00:00:57,320 --> 00:01:00,560 a clinical trial from start to finish. 21 00:01:00,560 --> 00:01:03,960 A world first look behind the scenes of what it takes to get 22 00:01:03,960 --> 00:01:05,440 a new drug to market. 23 00:01:07,880 --> 00:01:10,520 From the scientists who believe they have a breakthrough 24 00:01:10,520 --> 00:01:12,600 drug for Parkinson's... 25 00:01:12,600 --> 00:01:14,280 I know the drug works. 26 00:01:14,280 --> 00:01:17,200 It's more how do you get it in the right dose in the right place 27 00:01:17,200 --> 00:01:18,360 at the right time. 28 00:01:18,360 --> 00:01:21,640 ..to the volunteers who put their lives on the line 29 00:01:21,640 --> 00:01:23,120 for medical science. 30 00:01:23,120 --> 00:01:25,720 This chance doesn't come along to many people, 31 00:01:25,720 --> 00:01:28,840 to be part of a trial that could truly shift medicine. 32 00:01:30,000 --> 00:01:33,040 It's a double-blind, placebo-controlled trial 33 00:01:33,040 --> 00:01:37,240 where only half get the real drug and half just a placebo. 34 00:01:38,320 --> 00:01:41,320 No one knows who's getting what... 35 00:01:41,320 --> 00:01:42,840 ..not even the doctors. 36 00:01:42,840 --> 00:01:46,880 To have a huge operation like that and then have to have a placebo. 37 00:01:46,880 --> 00:01:48,280 Is that human? 38 00:01:48,280 --> 00:01:49,560 Not really, is it? 39 00:01:49,560 --> 00:01:51,560 Why do we do it? 40 00:01:51,560 --> 00:01:54,600 We want to live longer, that's the truth. 41 00:01:54,600 --> 00:01:58,200 For some, there are remarkable transformations... 42 00:01:58,200 --> 00:01:59,880 It was like a bloody miracle. 43 00:01:59,880 --> 00:02:02,080 Look at my hands, they're just... 44 00:02:02,080 --> 00:02:03,320 Look at that. 45 00:02:03,320 --> 00:02:06,360 ..for others disappointment and setback. 46 00:02:06,360 --> 00:02:07,720 I felt something as I went in. 47 00:02:07,720 --> 00:02:08,800 It felt like a vessel. 48 00:02:08,800 --> 00:02:10,760 You know what? I hope he's not on the drug. 49 00:02:10,760 --> 00:02:12,640 I thought I was going to die. 50 00:02:12,640 --> 00:02:16,520 If this is as good as it gets, I'd be pissed off. 51 00:02:16,520 --> 00:02:18,240 Could this be the miracle drug 52 00:02:18,240 --> 00:02:22,040 millions of Parkinson's sufferers worldwide have been waiting for? 53 00:02:22,040 --> 00:02:23,400 See you on the other side. 54 00:02:38,120 --> 00:02:43,320 Tom Isaacs, now 44, was 27 years old when he was diagnosed 55 00:02:43,320 --> 00:02:46,720 with Parkinson's, a disease of the brain that affects 56 00:02:46,720 --> 00:02:48,160 his ability to move. 57 00:02:51,680 --> 00:02:55,160 It's the world's second most common neurodegenerative condition 58 00:02:55,160 --> 00:03:01,000 after Alzheimer's, with around 145,000 sufferers in the UK. 59 00:03:03,600 --> 00:03:07,440 When I first was diagnosed, you wouldn't even know I had it 60 00:03:07,440 --> 00:03:11,960 and it was like that for about the first five, six years. 61 00:03:17,600 --> 00:03:20,480 Nowadays, everyone knows there's something going on. 62 00:03:23,360 --> 00:03:26,600 Inflicting Parkinson's on someone you love is tough. 63 00:03:27,640 --> 00:03:30,320 There are times when Lyndsey, I'm sure, thinks, 64 00:03:30,320 --> 00:03:32,480 "What on Earth am I doing with this loser? 65 00:03:35,320 --> 00:03:38,360 "He's just a shaking lump of jelly. 66 00:03:40,160 --> 00:03:42,560 "What does he give me back in return?" 67 00:03:42,560 --> 00:03:45,720 What do you think you give her back in return? 68 00:03:45,720 --> 00:03:46,800 Good looks. 69 00:03:48,480 --> 00:03:50,120 HE LAUGHS 70 00:03:52,400 --> 00:03:54,600 I'm very conscious of being looked at. 71 00:03:54,600 --> 00:03:56,000 People think I'm drunk. 72 00:03:57,880 --> 00:04:00,960 And taxis don't pick me up sometimes because they're seeing the disease, 73 00:04:00,960 --> 00:04:02,080 not the man. 74 00:04:06,600 --> 00:04:08,000 It's October 2012. 75 00:04:09,240 --> 00:04:11,080 The first day of the trial. 76 00:04:11,080 --> 00:04:13,720 Come in. Hi, Lucy. Hello, Tom. 77 00:04:13,720 --> 00:04:14,920 It's windy. 78 00:04:14,920 --> 00:04:15,920 Come on through. 79 00:04:15,920 --> 00:04:17,320 Thank you very much. 80 00:04:17,320 --> 00:04:20,000 I'm going to ask you to complete some questionnaires. OK. 81 00:04:20,000 --> 00:04:21,880 How are you feeling about the assessment? 82 00:04:21,880 --> 00:04:24,200 Yeah, OK. Not too bad. Yeah? 83 00:04:24,200 --> 00:04:25,520 Pretty cool. Good. 84 00:04:28,040 --> 00:04:32,000 Tom is one of almost 200 people with Parkinson's 85 00:04:32,000 --> 00:04:35,560 who've applied for the trial's 42 places... 86 00:04:35,560 --> 00:04:37,000 PHONE RINGS 87 00:04:37,000 --> 00:04:39,720 Hello. Parkinson's UK helpline, how can I help you? 88 00:04:39,720 --> 00:04:43,000 ..despite knowing that it involves complex brain surgery. 89 00:04:43,000 --> 00:04:47,000 Oh, is it the GDNF trial that you're interested in? 90 00:04:47,000 --> 00:04:51,800 This approach is novel and it's radical and I can't say 91 00:04:51,800 --> 00:04:56,040 it's without risk. We've done everything we can to minimise that. 92 00:04:57,320 --> 00:05:00,800 But, certainly, these are very brave people. 93 00:05:00,800 --> 00:05:04,280 Steve Gill will be doing all of the surgeries, 94 00:05:04,280 --> 00:05:05,720 but choosing the volunteers 95 00:05:05,720 --> 00:05:08,560 is down to movement disorder specialist Alan Whone, 96 00:05:08,560 --> 00:05:10,640 who's in overall charge of the trial. 97 00:05:15,280 --> 00:05:18,840 The situation in Parkinson's is that we have therapies 98 00:05:18,840 --> 00:05:22,160 that may help some of the symptoms, but, over time, 99 00:05:22,160 --> 00:05:24,880 people relentlessly progress. 100 00:05:27,280 --> 00:05:29,920 And we have no way of slowing that down and certainly no way 101 00:05:29,920 --> 00:05:33,400 of reversing it and so that's a great unmet need. 102 00:05:37,560 --> 00:05:41,760 What we're testing here is whether a drug called GDNF 103 00:05:41,760 --> 00:05:47,000 has the potential to restore brain cells in Parkinson's. 104 00:05:47,000 --> 00:05:48,560 What's your name? 105 00:05:48,560 --> 00:05:53,040 That would really be a game changer for people with the second commonest 106 00:05:53,040 --> 00:05:55,960 neurodegenerative condition in the world. 107 00:05:58,120 --> 00:06:04,120 The £3 million trial straddles two NHS hospitals in Bristol 108 00:06:04,120 --> 00:06:06,800 and is what's known as a Phase 2 trial. 109 00:06:09,440 --> 00:06:13,080 It's taken almost 20 years of laboratory work and animal studies 110 00:06:13,080 --> 00:06:14,560 to get GDNF this far. 111 00:06:16,280 --> 00:06:20,880 Now to become a licensed treatment, GDNF must perform better 112 00:06:20,880 --> 00:06:24,040 than a placebo drug in humans. 113 00:06:24,040 --> 00:06:26,760 OK, so, if you look my finger... You can call me Tom, by the way. 114 00:06:26,760 --> 00:06:28,400 OK, thanks, Tom. I'm Neil. 115 00:06:28,400 --> 00:06:32,080 We're looking for people between 35 and 75... 116 00:06:32,080 --> 00:06:34,280 You haven't got any pain in your arms and legs, have you? 117 00:06:34,280 --> 00:06:35,520 Not at the moment. 118 00:06:35,520 --> 00:06:37,720 ..that have moderate stage Parkinson's. 119 00:06:39,560 --> 00:06:41,560 That's brilliant. OK. Thank you very much. 120 00:06:41,560 --> 00:06:45,800 Now, Parkinson's is a disease of older people, commonly, 121 00:06:45,800 --> 00:06:48,320 but, against the public perception, 122 00:06:48,320 --> 00:06:51,600 there are many people who develop Parkinson's at a young age. 123 00:06:51,600 --> 00:06:54,680 If you just go across until you get to the very end, OK? 124 00:06:54,680 --> 00:06:58,280 The shortlisted volunteers now face a series of tests. 125 00:06:58,280 --> 00:07:00,480 Green, red, green, red, green... 126 00:07:00,480 --> 00:07:03,760 These are designed to assess their Parkinson's 127 00:07:03,760 --> 00:07:06,360 and to make sure they can cope, physically and psychologically, 128 00:07:06,360 --> 00:07:08,800 with the demands of the trial. 129 00:07:08,800 --> 00:07:10,760 Well done, you're doing really well. 130 00:07:11,760 --> 00:07:14,320 I respond well to praise. 131 00:07:14,320 --> 00:07:18,600 Parkinson's is a progressive neurodegenerative condition, 132 00:07:18,600 --> 00:07:24,040 which means that brain cells are dying off in a relentless fashion... 133 00:07:25,120 --> 00:07:27,440 One, two, three... 134 00:07:27,440 --> 00:07:31,440 ..in particular, types of brain cells that release a chemical 135 00:07:31,440 --> 00:07:35,320 called dopamine, which is necessary to allow movement. 136 00:07:35,320 --> 00:07:37,480 Keep on doing it until I say stop. 137 00:07:37,480 --> 00:07:42,160 Parkinson's comes with more than about 60 different symptoms. 138 00:07:42,160 --> 00:07:45,200 Movement symptoms, but on the other side, you've got lots of so-called 139 00:07:45,200 --> 00:07:49,320 non-movement symptoms that include memory and thinking problems, 140 00:07:49,320 --> 00:07:53,400 depression, anxiety, difficulties with sleep, problems with bladder 141 00:07:53,400 --> 00:07:54,720 and bowel and so on. 142 00:07:54,720 --> 00:07:56,880 So, there's four booklets to complete. Oh, OK. 143 00:07:56,880 --> 00:07:59,400 So, we start with number one, two, three, four, so working 144 00:07:59,400 --> 00:08:01,160 our way through them. There's quite a few. 145 00:08:01,160 --> 00:08:04,680 At 72, Ron Johnson is the oldest volunteer 146 00:08:04,680 --> 00:08:06,880 to be screened for the trial. 147 00:08:06,880 --> 00:08:08,840 Smell the box and then if you can 148 00:08:08,840 --> 00:08:12,240 shade in whether you think it's A, B, C or D, OK? 149 00:08:12,240 --> 00:08:13,600 Righto. 150 00:08:22,320 --> 00:08:23,880 I can put anything down? 151 00:08:23,880 --> 00:08:26,840 Yeah, what you think it smells of. 152 00:08:26,840 --> 00:08:29,640 Nothing. You can't smell anything at all? No. 153 00:08:31,160 --> 00:08:33,920 Losing your sense of smell is often one of the first 154 00:08:33,920 --> 00:08:36,360 symptoms of Parkinson's. 155 00:08:36,360 --> 00:08:40,360 If the new drug works, this could be one of the abilities to return. 156 00:08:42,440 --> 00:08:44,240 Oh, my, I can't smell bugger all. 157 00:08:55,080 --> 00:09:00,120 A retired aircraft engineer, Ron was diagnosed nine years ago. 158 00:09:00,120 --> 00:09:03,240 Grandad, you are very shaky. I am today. 159 00:09:03,240 --> 00:09:04,720 That's very true. 160 00:09:04,720 --> 00:09:07,040 Is it because you're worried or excited? 161 00:09:08,480 --> 00:09:10,960 He used to enjoy an active lifestyle, 162 00:09:10,960 --> 00:09:14,080 but Parkinson's has slowed him down a lot. 163 00:09:15,120 --> 00:09:16,560 That's it, just put a blob in each. 164 00:09:18,640 --> 00:09:23,920 His wife, May, has also noticed changes in his personality and mood. 165 00:09:23,920 --> 00:09:27,560 The person that I married and have lived with all these years 166 00:09:27,560 --> 00:09:31,280 is kind of slowly disappearing in a way. 167 00:09:31,280 --> 00:09:34,040 Open that. 168 00:09:34,040 --> 00:09:36,240 That's orange. Yellow. 169 00:09:38,000 --> 00:09:41,120 It's hoped the new drug might reverse the cognitive decline 170 00:09:41,120 --> 00:09:43,600 that's common in Parkinson's too. 171 00:09:43,600 --> 00:09:45,600 Take some of this, without shaking. 172 00:09:48,120 --> 00:09:50,520 And put it on top of the cake. You're the shaky one. 173 00:09:50,520 --> 00:09:52,000 Just let me do one more. 174 00:09:52,000 --> 00:09:56,160 The trial was something that he's chosen to do, so I'm kind 175 00:09:56,160 --> 00:09:58,040 of going along with it, really. 176 00:09:58,040 --> 00:10:02,480 I suppose hoping that I'd get the person back that he was. 177 00:10:02,480 --> 00:10:04,720 I really would like to do it. Why? 178 00:10:05,960 --> 00:10:10,320 The main reason is totally and absolutely selfish. 179 00:10:10,320 --> 00:10:14,240 I just want to play football with my grandkids. 180 00:10:16,240 --> 00:10:18,080 HE SNIFFS 181 00:10:25,400 --> 00:10:26,440 Silly, isn't it? 182 00:10:38,440 --> 00:10:42,040 Tom has been living with Parkinson's for 17 years. 183 00:10:43,400 --> 00:10:46,840 It is with you every single second of every day. 184 00:10:48,200 --> 00:10:50,920 It interferes with everything that people take for granted 185 00:10:50,920 --> 00:10:52,200 in their lives. 186 00:10:52,200 --> 00:10:54,840 Movement, eating food, writing. 187 00:10:54,840 --> 00:10:57,560 You know, just simple things. 188 00:10:57,560 --> 00:11:01,120 The most obvious symptoms of Parkinson's are slowness, 189 00:11:01,120 --> 00:11:02,560 rigidity and tremor. 190 00:11:04,640 --> 00:11:07,480 Initially on one side of the body, but, eventually, both. 191 00:11:11,760 --> 00:11:15,680 Tom takes drugs that boost the amount of dopamine in his brain, 192 00:11:15,680 --> 00:11:21,120 but they don't always work and can cause considerable side effects. 193 00:11:21,120 --> 00:11:23,880 So, actually I've got too much movement 194 00:11:23,880 --> 00:11:28,000 and it's involuntary movement which I can't control. 195 00:11:30,240 --> 00:11:33,880 The longer you have Parkinson's, the worse it gets. 196 00:11:35,640 --> 00:11:36,920 So, what's the best plan? 197 00:11:38,600 --> 00:11:41,640 My days, there's no rhyme or reason to them. 198 00:11:41,640 --> 00:11:45,480 I can spend the day in perfect harmony with my body. 199 00:11:45,480 --> 00:11:47,120 Pretty rare these days. 200 00:11:47,120 --> 00:11:49,120 OK. Thanks. Thanks a lot. 201 00:11:49,120 --> 00:11:53,440 Or I can spend the day, seven hours, shaking on the floor. 202 00:11:55,240 --> 00:11:56,200 Oh, God. 203 00:12:06,200 --> 00:12:08,360 Inside our brains we've got two types of cells. 204 00:12:08,360 --> 00:12:11,680 One are the neurons, which do the information processing, 205 00:12:11,680 --> 00:12:14,360 and the other ones are glial cells and these are supporting 206 00:12:14,360 --> 00:12:17,160 cells, but they're critically important for hardwiring 207 00:12:17,160 --> 00:12:19,200 and maintaining our brains 208 00:12:19,200 --> 00:12:24,040 and a key thing that they do is release growth factors. 209 00:12:24,040 --> 00:12:26,240 One of these growth factors is called 210 00:12:26,240 --> 00:12:31,000 glial cell-derived neurotrophic factor, GDNF. 211 00:12:32,200 --> 00:12:35,040 Very shortly after it was discovered, it was seen it had 212 00:12:35,040 --> 00:12:37,520 enormous potential to treat Parkinson's disease. 213 00:12:40,600 --> 00:12:45,040 In the lab, it was found that at high concentrations, GDNF 214 00:12:45,040 --> 00:12:48,720 could regenerate dopamine brain cells, the ones that die 215 00:12:48,720 --> 00:12:51,280 in Parkinson's, affecting the ability to move. 216 00:12:56,360 --> 00:12:58,200 In 2001, 217 00:12:58,200 --> 00:13:01,840 Steve Gill became the first to successfully deliver a therapeutic 218 00:13:01,840 --> 00:13:05,560 dose of GDNF to people with Parkinson's 219 00:13:05,560 --> 00:13:09,160 using a tiny tube inserted directly into the brain. 220 00:13:10,600 --> 00:13:12,640 Well, it was pretty astonishing, really. 221 00:13:12,640 --> 00:13:15,240 We saw quite remarkable changes occurring quickly. 222 00:13:18,520 --> 00:13:23,720 And it wasn't just in the movement of the patients and their stability, 223 00:13:23,720 --> 00:13:26,760 but also in their well-being and cognitive function. 224 00:13:26,760 --> 00:13:28,680 So, everything improved 225 00:13:28,680 --> 00:13:32,360 and this is something that, you know, had never been seen before. 226 00:13:32,360 --> 00:13:37,600 Steve's findings electrified neuroscience and in 2004, a major 227 00:13:37,600 --> 00:13:41,240 drug company took GDNF on to a Phase 2 trial 228 00:13:41,240 --> 00:13:42,680 with more patients. 229 00:13:44,720 --> 00:13:47,920 But it was stopped early when very high doses of the drug 230 00:13:47,920 --> 00:13:50,960 given to monkeys caused damage to their brains. 231 00:13:53,080 --> 00:13:56,400 The drug company also reported that GDNF had performed no better 232 00:13:56,400 --> 00:14:01,320 than a placebo, something all drugs must do to be licensed. 233 00:14:01,320 --> 00:14:04,640 Steve Gill's treatment was dropped. 234 00:14:04,640 --> 00:14:07,480 Even though it was very bad news, 235 00:14:07,480 --> 00:14:11,120 I knew absolutely that this was a drug that was going to do the job. 236 00:14:13,880 --> 00:14:17,200 Having seen the remarkable effects, that wasn't going to stop me 237 00:14:17,200 --> 00:14:20,560 and I knew there were things wrong with the way they were doing it 238 00:14:20,560 --> 00:14:23,720 and I already had in mind ways of improving the delivery 239 00:14:23,720 --> 00:14:26,480 which was a critical element. 240 00:14:26,480 --> 00:14:30,360 It's taken an international team of scientists seven years to resolve 241 00:14:30,360 --> 00:14:33,880 the safety issues and to secure the key regulatory and ethics 242 00:14:33,880 --> 00:14:36,960 approvals necessary to try GDNF in people again. 243 00:14:38,720 --> 00:14:40,560 I know the drug works. 244 00:14:40,560 --> 00:14:43,400 It's a matter of how do you get it in the right dose in the right 245 00:14:43,400 --> 00:14:44,760 place at the right time. 246 00:14:50,120 --> 00:14:53,560 From the almost 200 who have applied, the Bristol team 247 00:14:53,560 --> 00:14:57,600 is now ready to offer 42 volunteers a place on the trial. 248 00:14:59,680 --> 00:15:02,560 Take a seat. Come and have a seat. 249 00:15:02,560 --> 00:15:04,960 Good to see you. 250 00:15:07,800 --> 00:15:09,480 Good. How are you? 251 00:15:09,480 --> 00:15:10,680 I'm fine. 252 00:15:10,680 --> 00:15:12,840 I'm sure you've had time to reflect. 253 00:15:12,840 --> 00:15:14,920 Very much so and I want to do it. 254 00:15:14,920 --> 00:15:16,960 I want to go ahead and I want to do it. 255 00:15:16,960 --> 00:15:22,880 OK. So, subject to the MRI scan, which is the next part, not showing 256 00:15:22,880 --> 00:15:25,640 anything untoward in your brain which we're not expecting, 257 00:15:25,640 --> 00:15:29,080 we'll be very happy to put you forward for the study, 258 00:15:29,080 --> 00:15:30,920 if you would like to take part. 259 00:15:32,880 --> 00:15:35,200 If that's what you'd like to hear. 260 00:15:42,920 --> 00:15:44,880 Yes. OK. 261 00:15:44,880 --> 00:15:46,120 I'm delighted. That's great. 262 00:15:46,120 --> 00:15:48,960 Thank you very much. I look forward to seeing you probably next week. 263 00:15:48,960 --> 00:15:50,200 I'll be here. 264 00:15:50,200 --> 00:15:52,360 Thank you very much. 265 00:15:52,360 --> 00:15:53,880 Thanks. Love you to bits. 266 00:15:53,880 --> 00:15:55,000 Well done. 267 00:15:56,640 --> 00:15:58,680 And you. Bye-bye, Ron. 268 00:15:58,680 --> 00:16:00,160 I'll see you next time you come. 269 00:16:00,160 --> 00:16:01,280 I'll come see you out. OK. 270 00:16:05,640 --> 00:16:07,480 Come on. 271 00:16:07,480 --> 00:16:08,520 Wow, it's windy. 272 00:16:10,560 --> 00:16:14,680 Kay Cotton, an artist from Cornwall, is also offered a place. 273 00:16:15,840 --> 00:16:17,880 This trial is so I can fight the war. 274 00:16:17,880 --> 00:16:21,960 You know, I can't do other things, but I can do this. 275 00:16:21,960 --> 00:16:26,600 I'm giving you my body and I want you to find the cure. 276 00:16:40,200 --> 00:16:43,440 At 41, Nick Vallotton is the youngest volunteer 277 00:16:43,440 --> 00:16:45,040 to be accepted onto the trial. 278 00:16:49,000 --> 00:16:52,400 I went to see an osteopath in London for what I thought was a shoulder 279 00:16:52,400 --> 00:16:56,320 injury and he said, "Is your writing getting smaller?" 280 00:16:56,320 --> 00:16:59,120 And I said, "Yeah, it is." 281 00:16:59,120 --> 00:17:01,920 And he said, "Well, small writing, stiff shoulder. 282 00:17:01,920 --> 00:17:03,960 "Have you ever thought about Parkinson's?" 283 00:17:03,960 --> 00:17:06,720 And this was a good two years 284 00:17:06,720 --> 00:17:09,560 before I saw anybody else about the whole thing 285 00:17:09,560 --> 00:17:12,080 and I just shrugged it off and went, "No." 286 00:17:12,080 --> 00:17:14,280 You know? "It's not Parkinson's." 287 00:17:20,840 --> 00:17:24,120 I'm in what they call my honeymoon period, 288 00:17:24,120 --> 00:17:26,000 which sounds very nice. 289 00:17:30,160 --> 00:17:32,320 My symptoms aren't too bad. 290 00:17:32,320 --> 00:17:34,520 The drugs are working quite well. 291 00:17:34,520 --> 00:17:39,360 But like all degenerative neurological conditions, 292 00:17:39,360 --> 00:17:41,760 the future is quite bleak, you know. 293 00:17:44,640 --> 00:17:47,040 I'm doing the trial because 294 00:17:47,040 --> 00:17:52,480 if the trial does end up offering physiological benefits, 295 00:17:52,480 --> 00:17:55,600 then getting those at 41 296 00:17:55,600 --> 00:17:57,880 is probably better than getting them at 51. 297 00:18:04,720 --> 00:18:09,160 For Tom, volunteering for the trial is the culmination of a quest 298 00:18:09,160 --> 00:18:11,200 that started seven years ago. 299 00:18:13,960 --> 00:18:16,920 Morning! Morning! 300 00:18:16,920 --> 00:18:20,400 Yeah, I think you said the majority of the Parkinson's commentators... 301 00:18:20,400 --> 00:18:24,440 In 2005, he gave up his career as a surveyor 302 00:18:24,440 --> 00:18:26,840 and founded the Cure Parkinson's Trust 303 00:18:26,840 --> 00:18:28,640 to lobby for a cure. 304 00:18:33,880 --> 00:18:37,440 But having had Parkinson's for 17 years, 305 00:18:37,440 --> 00:18:41,480 it may be too late for Tom himself to take part in the trial. 306 00:18:41,480 --> 00:18:43,960 You want them to have enough symptoms 307 00:18:43,960 --> 00:18:47,560 that you can see improvement, but at the same time, 308 00:18:47,560 --> 00:18:53,160 not be so advanced that they have a lack of brain cells left 309 00:18:53,160 --> 00:18:55,720 to actually regenerate. 310 00:18:55,720 --> 00:18:59,960 Tonight, Tom is staying in a hotel in Bristol close to the hospital. 311 00:18:59,960 --> 00:19:03,480 Everything now depends on one final test tomorrow. 312 00:19:03,480 --> 00:19:05,960 I'm taking this pill. This is Sinemet. 313 00:19:05,960 --> 00:19:08,720 It's a drug that helps me move. 314 00:19:08,720 --> 00:19:11,040 And this is the last one I'm going to take of these 315 00:19:11,040 --> 00:19:13,800 for the next 18 hours, I should think. 316 00:19:13,800 --> 00:19:17,040 Normally, Tom would take a dose in the morning, 317 00:19:17,040 --> 00:19:21,200 but the team needs to measure what his Parkinson's is like without it. 318 00:19:21,200 --> 00:19:24,160 And this'll be the longest period I've not taken drugs for 319 00:19:24,160 --> 00:19:25,840 for about 15 years. 320 00:19:25,840 --> 00:19:28,560 So, this is going to be quite a shock, I should imagine, 321 00:19:28,560 --> 00:19:29,960 as to how I'm going to feel. 322 00:19:29,960 --> 00:19:32,200 INTERVIEWER: Do you have a picture in your head 323 00:19:32,200 --> 00:19:36,320 of what life would be like if you get on the trial and GDNF works? 324 00:19:40,240 --> 00:19:42,440 Such an emotional question, really. 325 00:19:45,680 --> 00:19:48,120 I can think of so many places that I'd be. 326 00:19:59,160 --> 00:20:04,040 8:00am, and it's 14 hours since Tom had any medication. 327 00:20:14,520 --> 00:20:17,480 His symptoms are significantly worse than he expected. 328 00:20:28,680 --> 00:20:31,880 For the first time ever, Tom has to accept a wheelchair 329 00:20:31,880 --> 00:20:34,600 to get him into the hospital's photographic studio. 330 00:20:36,800 --> 00:20:40,920 Here, his baseline Parkinson's will be videoed and scored. 331 00:20:40,920 --> 00:20:42,920 You can look at the camera and tell us 332 00:20:42,920 --> 00:20:45,400 just when you were diagnosed with the Parkinson's 333 00:20:45,400 --> 00:20:47,800 and what your first symptoms were, please. 334 00:20:47,800 --> 00:20:49,880 I was diagnosed in 1996. 335 00:20:49,880 --> 00:20:52,920 My first symptoms were a tremor in my right hand. 336 00:20:52,920 --> 00:20:54,920 Coming off their medication for patients 337 00:20:54,920 --> 00:20:56,800 can be quite a shock the first time. 338 00:20:56,800 --> 00:21:00,240 They don't realise how dependent on the tablets they are. 339 00:21:00,240 --> 00:21:01,520 Smile. 340 00:21:05,080 --> 00:21:07,000 Best I can do. 341 00:21:07,000 --> 00:21:10,200 We can see just how stiff and slow they are, 342 00:21:10,200 --> 00:21:12,800 which is reflective of how little dopamine 343 00:21:12,800 --> 00:21:15,880 their brain cells may be making. 344 00:21:15,880 --> 00:21:18,680 And then we can measure that severity 345 00:21:18,680 --> 00:21:21,320 by having them do certain movements. 346 00:21:28,360 --> 00:21:30,680 Well done. It does seem almost cruel 347 00:21:30,680 --> 00:21:33,320 to ask people to stop their medication overnight 348 00:21:33,320 --> 00:21:36,200 and then see them in distress and then see them struggling, 349 00:21:36,200 --> 00:21:40,760 but at the present time, it's felt that that's the best way 350 00:21:40,760 --> 00:21:43,280 of really understanding what's happening 351 00:21:43,280 --> 00:21:45,440 at a movement level. 352 00:21:45,440 --> 00:21:47,760 I think, though, through the screening visits - 353 00:21:47,760 --> 00:21:50,600 both the outpatient screen and the inpatient screen - 354 00:21:50,600 --> 00:21:53,240 we've probably been looking at you for about 30 hours, 355 00:21:53,240 --> 00:21:57,720 and I can say that you're at the more severe end 356 00:21:57,720 --> 00:22:03,120 of the inclusion criteria, but you fall within those criteria, 357 00:22:03,120 --> 00:22:05,840 and therefore, we'd be very happy to include you, 358 00:22:05,840 --> 00:22:09,200 and look forward to seeing you shortly 359 00:22:09,200 --> 00:22:11,520 for the next part, which is the MRI scan. 360 00:22:13,360 --> 00:22:17,320 Excellent. Very good news. Very good news. Very good news. 361 00:22:17,320 --> 00:22:18,920 Thank you. 362 00:22:18,920 --> 00:22:23,120 Do you have any questions about what we've spoken about? 363 00:22:23,120 --> 00:22:27,280 I must say, I'm quite surprised. It's been quite a tough call cos... 364 00:22:27,280 --> 00:22:31,360 Quite a tight one, but I'm delighted. Yeah. 365 00:22:32,840 --> 00:22:35,880 Tom can now join the other 41 volunteers 366 00:22:35,880 --> 00:22:38,120 accepted onto the trial. 367 00:22:38,120 --> 00:22:41,400 All of them will repeat these tests every eight weeks, 368 00:22:41,400 --> 00:22:44,640 helping the team work out how much improvement, if any, 369 00:22:44,640 --> 00:22:46,840 they make during the course of the trial. 370 00:22:51,960 --> 00:22:56,000 Around 1,000 clinical drugs trials take place in Britain every year, 371 00:22:56,000 --> 00:22:58,440 but this one is especially controversial... 372 00:22:59,880 --> 00:23:02,480 ..not just because GDNF has failed before... 373 00:23:02,480 --> 00:23:03,720 Open your eyes. 374 00:23:03,720 --> 00:23:06,360 ..but because you cannot give GDNF in a pill 375 00:23:06,360 --> 00:23:09,080 or via injection into the bloodstream. 376 00:23:09,080 --> 00:23:12,080 If you want to get GDNF into the brain, 377 00:23:12,080 --> 00:23:14,640 you need to give it by surgical delivery - 378 00:23:14,640 --> 00:23:17,160 a main line, if you like, 379 00:23:17,160 --> 00:23:20,800 direct to the part of the brain where you want it to go. 380 00:23:20,800 --> 00:23:24,880 In a world first, the Bristol team will implant four catheters 381 00:23:24,880 --> 00:23:28,680 deep into the brains of 42 people with Parkinson's 382 00:23:28,680 --> 00:23:31,760 and infuse GDNF or placebo 383 00:23:31,760 --> 00:23:34,520 through a port in the side of their heads. 384 00:23:40,920 --> 00:23:45,080 The device has been developed here in Gloucestershire by Steve Gill, 385 00:23:45,080 --> 00:23:48,080 working with some of the world's leading medical engineers. 386 00:23:52,680 --> 00:23:54,240 One of the big challenges we face 387 00:23:54,240 --> 00:23:56,960 in treating neurological disease, such as Parkinson's disease, 388 00:23:56,960 --> 00:23:59,760 is that there's a naturally occurring barrier 389 00:23:59,760 --> 00:24:02,800 between the bloodstream and the brain, 390 00:24:02,800 --> 00:24:05,400 which prevents poisons going across 391 00:24:05,400 --> 00:24:07,640 from the bloodstream into the brain to protect us, 392 00:24:07,640 --> 00:24:10,920 but equally, it stops many drugs going across. 393 00:24:12,560 --> 00:24:15,200 So, when GDNF was discovered and shown to have 394 00:24:15,200 --> 00:24:20,160 these amazing effects on restoring the function of dying nerve cells, 395 00:24:20,160 --> 00:24:22,160 the next thing was how do you deliver the drug 396 00:24:22,160 --> 00:24:26,000 into a deep part of the brain, which deteriorates in Parkinson's, 397 00:24:26,000 --> 00:24:28,400 every month for the lifetime of the patient? 398 00:24:29,840 --> 00:24:34,720 Steve's solution is to use a method called convection enhanced delivery. 399 00:24:34,720 --> 00:24:39,600 This is where we push fluid through a tiny tube very, very slowly. 400 00:24:39,600 --> 00:24:42,240 And if we do it just at the right flow rate, 401 00:24:42,240 --> 00:24:45,880 we can start to drive the drug between the cells of the brain 402 00:24:45,880 --> 00:24:48,520 and push it out over quite big volumes. 403 00:24:48,520 --> 00:24:50,440 It's quite a complicated thing to do 404 00:24:50,440 --> 00:24:53,040 down multiple tubes that we felt we needed to have, 405 00:24:53,040 --> 00:24:56,680 and therefore we had to design completely new technology. 406 00:24:56,680 --> 00:24:59,120 Every element of the device is unique, 407 00:24:59,120 --> 00:25:03,560 from the 5mm port that has been 3-D printed from titanium powder 408 00:25:03,560 --> 00:25:08,680 to the tiny catheters which will be inserted 8cm into the brain. 409 00:25:09,880 --> 00:25:13,880 We're asking people to have experimental brain surgery, 410 00:25:13,880 --> 00:25:16,760 we're asking people to have an experimental device 411 00:25:16,760 --> 00:25:19,000 inserted into their heads, 412 00:25:19,000 --> 00:25:22,640 and we're asking people to have an experimental drug. 413 00:25:22,640 --> 00:25:25,400 We could do great harm here 414 00:25:25,400 --> 00:25:27,920 and we could genuinely make people worse 415 00:25:27,920 --> 00:25:29,760 than they were before they started. 416 00:25:35,600 --> 00:25:38,720 One of the first to have surgery will be Chris Brownbill, 417 00:25:38,720 --> 00:25:41,960 who was diagnosed with Parkinson's seven years ago. 418 00:25:41,960 --> 00:25:45,760 Yeah, yeah, yeah. I'm just coming down tonight. 419 00:25:45,760 --> 00:25:47,880 Chris is on his way to Bristol today. 420 00:25:49,360 --> 00:25:52,160 OK, that's great. Thanks for that. 421 00:25:52,160 --> 00:25:54,360 When he actually went through this trial, 422 00:25:54,360 --> 00:25:56,800 it was quite a big shock to us all. 423 00:26:00,640 --> 00:26:02,680 When he came back and said, "Ooh, yes, 424 00:26:02,680 --> 00:26:05,320 "they've got to do this in my brain and they've got to do that," 425 00:26:05,320 --> 00:26:07,880 straight away, I thought, "No, I don't want him to do it." 426 00:26:09,160 --> 00:26:15,320 I tend to do things and then worry about the consequences later. 427 00:26:15,320 --> 00:26:17,320 So, basically, I got onto this trial, 428 00:26:17,320 --> 00:26:18,800 so I'm doing this trial. That was it. 429 00:26:18,800 --> 00:26:20,320 There was no discussion at all. 430 00:26:21,800 --> 00:26:24,840 I'm all packed and ready to go, basically. 431 00:26:24,840 --> 00:26:28,440 And I have to say that, you know, the girls were a bit dubious 432 00:26:28,440 --> 00:26:30,080 and saying, "No, Dad, don't do it." 433 00:26:30,080 --> 00:26:32,600 See you later, Abby. Good luck. 434 00:26:32,600 --> 00:26:34,960 He's the one that's determined to do it. 435 00:26:34,960 --> 00:26:37,200 I'm coming down with you. THEY LAUGH 436 00:26:37,200 --> 00:26:40,480 See you. Bye, darling. I love you. Love you, too. 437 00:26:40,480 --> 00:26:43,480 And I'll see you tomorrow. All right, good luck. 438 00:26:50,880 --> 00:26:52,880 It's three days before Christmas 439 00:26:52,880 --> 00:26:56,480 and the surgeries to fit the ports are about to begin. 440 00:26:59,040 --> 00:27:01,400 You OK? Glamorous. 441 00:27:03,640 --> 00:27:07,080 The procedure involves two general anaesthetics, 442 00:27:07,080 --> 00:27:09,920 and this is the first, for an MRI scan 443 00:27:09,920 --> 00:27:13,440 to map the geography of Tom's brain to submillimetre accuracy. 444 00:27:13,440 --> 00:27:17,120 BEEPING 445 00:27:17,120 --> 00:27:23,360 So, today, these scans are used for planning the operation tomorrow. 446 00:27:23,360 --> 00:27:28,280 We want to see the location of this structure. 447 00:27:28,280 --> 00:27:30,440 Steve will implant the catheters 448 00:27:30,440 --> 00:27:34,400 into a walnut-sized part of Tom's brain called the putamen. 449 00:27:34,400 --> 00:27:37,560 And we need to determine the trajectory, the path 450 00:27:37,560 --> 00:27:40,120 by which they can travel to get there safely. 451 00:27:40,120 --> 00:27:44,480 The hope is that GDNF will cause the surviving dopamine neurons 452 00:27:44,480 --> 00:27:47,920 in the putamen to regrow and start producing more dopamine, 453 00:27:47,920 --> 00:27:50,360 reversing the effects of Parkinson's. 454 00:27:50,360 --> 00:27:52,200 It should make a big difference to them, 455 00:27:52,200 --> 00:27:53,760 if we got all the bits right. 456 00:27:55,200 --> 00:27:57,720 INTERVIEWER: Is that a big "if"? No. 457 00:28:01,920 --> 00:28:06,000 We're going into the most vascular structure in the body. 458 00:28:06,000 --> 00:28:09,000 It's got more blood vessels per cubic millimetre than anywhere else, 459 00:28:09,000 --> 00:28:11,200 so it's a highly risky place to go. 460 00:28:12,920 --> 00:28:14,320 Come on through. 461 00:28:16,040 --> 00:28:18,200 The biggest risk from the procedure is, 462 00:28:18,200 --> 00:28:22,760 when we put these catheters in, that we could hit a blood vessel, 463 00:28:22,760 --> 00:28:24,280 and of course, bleeding. 464 00:28:24,280 --> 00:28:26,560 And that's the biggest risk to you. OK. 465 00:28:26,560 --> 00:28:29,280 And the consequence of that could be quite serious, 466 00:28:29,280 --> 00:28:32,240 in terms of having a stroke, effectively. Yeah. 467 00:28:32,240 --> 00:28:34,640 So, that's the biggest concern. 468 00:28:34,640 --> 00:28:37,680 Then the other bits which are relevant is, 469 00:28:37,680 --> 00:28:39,800 because you've got a cardiac stent... Right. 470 00:28:39,800 --> 00:28:42,760 ..you had cardiac problems, that, you know, 471 00:28:42,760 --> 00:28:44,560 that still is there in the background, 472 00:28:44,560 --> 00:28:46,600 and when you're undergoing a long anaesthetic, 473 00:28:46,600 --> 00:28:49,040 you have a risk of cardiac problems relating to that. 474 00:28:49,040 --> 00:28:51,440 And we've taken you off your aspirin... Yeah. 475 00:28:51,440 --> 00:28:54,560 ..so you have an increased risk of getting a clot. 476 00:28:54,560 --> 00:28:56,680 OK. But we had to do that. 477 00:28:56,680 --> 00:28:59,160 Otherwise, you'd have an increased risk of bleeding. 478 00:28:59,160 --> 00:29:01,800 So, it's kind of one of those balance things. 479 00:29:01,800 --> 00:29:03,120 Yeah, all right. Yeah? 480 00:29:03,120 --> 00:29:05,600 All right? OK. OK. Anything you want to go through? 481 00:29:05,600 --> 00:29:07,800 I can't think of anything right now, no. 482 00:29:07,800 --> 00:29:10,120 It's a long day. Yeah, yeah, yeah. 483 00:29:10,120 --> 00:29:12,800 But if it goes till whenever, don't worry. OK. 484 00:29:12,800 --> 00:29:15,040 That's just how things work, you know. OK. 485 00:29:15,040 --> 00:29:18,320 I'll try not to worry. All right, OK. See you. Thank you. 486 00:29:22,320 --> 00:29:24,200 Which way? This way? 487 00:29:30,280 --> 00:29:32,320 See you. OK. 488 00:29:39,640 --> 00:29:41,840 NURSE: We'll look after him. Thank you. 489 00:29:45,120 --> 00:29:47,240 It's all right. It's all right, darling. 490 00:29:47,240 --> 00:29:49,960 We'll take good care of him. Promise. I know you will. Thank you. 491 00:29:49,960 --> 00:29:51,320 Come on. Let's get you... 492 00:29:51,320 --> 00:29:53,000 Do you need a cup of tea or anything? 493 00:29:57,120 --> 00:30:00,360 Do you have any crowned, capped or loose teeth in the front there? No? 494 00:30:00,360 --> 00:30:02,600 And when did you last eat or drink something? 495 00:30:02,600 --> 00:30:05,080 Yesterday at midnight. Midnight. Smashing. OK. 496 00:30:05,080 --> 00:30:07,760 Tom is taken down to surgery. 497 00:30:07,760 --> 00:30:11,360 It's known that stress often makes symptoms worse. 498 00:30:11,360 --> 00:30:14,640 You'll just feel slightly woozy in a minute or two. 499 00:30:14,640 --> 00:30:17,960 See you on the other side. Yeah. You'll be fine. 500 00:30:24,160 --> 00:30:25,960 Feeling good. It's good, isn't it? 501 00:30:32,160 --> 00:30:34,480 OK. Bye. 502 00:30:43,760 --> 00:30:47,480 We're fitting on a reference frame so that when we do an image, 503 00:30:47,480 --> 00:30:51,480 we can effectively put a scale on to the position of the brain 504 00:30:51,480 --> 00:30:54,600 within the reference frame, 505 00:30:54,600 --> 00:30:58,040 and that's what we use to guide our instruments to the target. 506 00:30:58,040 --> 00:31:01,080 It looks fairly gruesome, fairly medieval, 507 00:31:01,080 --> 00:31:04,520 but obviously, we have to fix his head very rigidly, 508 00:31:04,520 --> 00:31:07,520 if you're machining the skull or doing anything, 509 00:31:07,520 --> 00:31:09,600 to ensure the whole thing is stable. 510 00:31:10,640 --> 00:31:13,680 Computer software developed especially for the trial 511 00:31:13,680 --> 00:31:16,720 combines the MRI scan Tom had yesterday 512 00:31:16,720 --> 00:31:21,240 with a CT scan to build a 3-D image of his brain. 513 00:31:21,240 --> 00:31:26,840 This is the putamen, which this software automatically detected. 514 00:31:28,080 --> 00:31:29,520 And we need to... 515 00:31:29,520 --> 00:31:31,760 These are our catheters that we need to deliver 516 00:31:31,760 --> 00:31:33,000 into the back part. 517 00:31:33,000 --> 00:31:35,640 This is the motor part of the structure, 518 00:31:35,640 --> 00:31:39,440 and you can see the catheters there. 519 00:31:39,440 --> 00:31:43,120 The 3-D image maps every detail of Tom's brain. 520 00:31:43,120 --> 00:31:45,960 Yeah, you can see every single blood vessel that you want to avoid, 521 00:31:45,960 --> 00:31:47,640 and it's quite a tangle, as you can see, 522 00:31:47,640 --> 00:31:50,200 that we need to miss to hit this target. 523 00:31:50,200 --> 00:31:52,480 But by having all this information, 524 00:31:52,480 --> 00:31:54,960 we can determine exactly where to go. 525 00:31:54,960 --> 00:31:57,560 This is our target - our deep target. 526 00:32:06,480 --> 00:32:10,120 A 12cm incision along Tom's centre parting line 527 00:32:10,120 --> 00:32:12,240 marks the start of the procedure. 528 00:32:14,760 --> 00:32:18,080 The team has spent many months planning for the surgeries, 529 00:32:18,080 --> 00:32:20,280 but it is still a leap into the unknown. 530 00:32:22,320 --> 00:32:25,960 It's the first time the operation has been performed on humans. 531 00:32:28,040 --> 00:32:31,680 Almost everything about the procedure is ground-breaking, 532 00:32:31,680 --> 00:32:37,360 from bespoke instrumentation to the use of a surgical robot. 533 00:32:37,360 --> 00:32:41,240 You wouldn't get on a jumbo jet without an autopilot. 534 00:32:41,240 --> 00:32:44,280 However good the pilot was, you would not... You'd be crazy. 535 00:32:44,280 --> 00:32:47,320 A robot works at very, very fine tolerances, 536 00:32:47,320 --> 00:32:50,760 fractions of a millimetre, and it does it very quickly. 537 00:32:50,760 --> 00:32:53,200 Guided by computer software, 538 00:32:53,200 --> 00:32:56,160 the robot ensures the entry point into Tom's skull 539 00:32:56,160 --> 00:32:58,480 is at exactly the right angle. 540 00:32:58,480 --> 00:33:02,320 A fraction of a millimetre out and they will miss their target. 541 00:33:05,000 --> 00:33:09,400 Steve drills through Tom's skull to the surface of the brain. 542 00:33:10,480 --> 00:33:13,120 Right. So, that's through now. 543 00:33:13,120 --> 00:33:17,840 We're now going to advance a probe - a rigid tungsten carbide probe - 544 00:33:17,840 --> 00:33:20,040 down to the top of the putamen, 545 00:33:20,040 --> 00:33:22,000 the part of the brain we want to treat. 546 00:33:31,800 --> 00:33:34,440 The process is repeated three times 547 00:33:34,440 --> 00:33:37,280 to create channels for all four catheters. 548 00:33:41,920 --> 00:33:44,200 Tom then has a CT scan 549 00:33:44,200 --> 00:33:46,360 to check that everything is in the right place. 550 00:33:48,280 --> 00:33:53,520 So, the green outline is where our plan for the catheter was, 551 00:33:53,520 --> 00:33:57,360 and the white shadow behind it is where the actual placement is. 552 00:33:57,360 --> 00:34:01,240 So, the width of this is 0.6mm. 553 00:34:01,240 --> 00:34:04,120 So, we've got 7mm accuracy, 554 00:34:04,120 --> 00:34:06,680 which is what we were hoping for on this catheter. 555 00:34:09,160 --> 00:34:12,320 Hello. I'm Dr Dunnet. I'm one of the anaesthetists. Have a seat. 556 00:34:12,320 --> 00:34:15,680 Every surgery has to be planned individually... 557 00:34:15,680 --> 00:34:17,760 Any loose teeth? 558 00:34:17,760 --> 00:34:19,080 Here it goes. 559 00:34:19,080 --> 00:34:21,360 ..and each takes the best part of a day. 560 00:34:21,360 --> 00:34:24,000 She'll send you off to sleep now, all right? OK. 561 00:34:24,000 --> 00:34:26,720 You've done ever so well. Thank you. 562 00:34:30,480 --> 00:34:33,360 The most technically demanding part of the procedure 563 00:34:33,360 --> 00:34:36,600 is fixing the port into the skull behind the ear. 564 00:34:38,640 --> 00:34:41,000 Firstly, it needs to be rigidly fixed to the bone, 565 00:34:41,000 --> 00:34:44,840 and the bone behind the ear can be quite thin in some cases. 566 00:34:44,840 --> 00:34:48,600 It needs to be very stable because we're fixing equipment to it. 567 00:34:48,600 --> 00:34:52,280 And if you get it wrong, there's a risk of infection, 568 00:34:52,280 --> 00:34:55,440 and that could be potentially life-threatening 569 00:34:55,440 --> 00:34:57,080 if it tracks into the brain. 570 00:34:57,080 --> 00:34:58,480 A wash here, please. 571 00:34:59,760 --> 00:35:01,720 After seven hours of prep, 572 00:35:01,720 --> 00:35:05,040 the time has come to implant the device. 573 00:35:05,040 --> 00:35:06,920 So, we're going right posterior. 574 00:35:12,160 --> 00:35:15,760 The catheters are fed down the four channels created earlier 575 00:35:15,760 --> 00:35:17,440 and secured into place. 576 00:35:17,440 --> 00:35:19,040 Big wash, please. 577 00:35:21,480 --> 00:35:24,520 Neil, can you put the port itself in there? 578 00:35:24,520 --> 00:35:26,160 The final part of the procedure 579 00:35:26,160 --> 00:35:30,040 is to seat the port in the hole created earlier. 580 00:35:30,040 --> 00:35:34,440 It connects to the catheters via a line fed under the scalp. 581 00:35:39,920 --> 00:35:43,080 Tom, how are you feeling? 582 00:35:43,080 --> 00:35:45,240 Well, I'm alive. 583 00:35:45,240 --> 00:35:47,000 You're alive. You survived it all. 584 00:35:47,000 --> 00:35:50,120 It all went very well, actually, so we're all very pleased. 585 00:35:51,360 --> 00:35:53,760 INTERVIEWER: Can you tell how you're feeling or not? 586 00:35:53,760 --> 00:35:57,600 Elation. Pure, massive elation. 587 00:36:06,040 --> 00:36:07,960 That went really well, actually. 588 00:36:07,960 --> 00:36:11,160 You've just got to get the juice now. Yeah. Yeah? 589 00:36:11,160 --> 00:36:14,280 All right. Anyway, I think you're going to head back to the ward now. 590 00:36:14,280 --> 00:36:16,480 Oh, by the way, what's that tattoo? 591 00:36:16,480 --> 00:36:20,280 The one item that I'm missing in my putamen - dopamine. 592 00:36:20,280 --> 00:36:22,600 Is it really? Is that what it is? 593 00:36:24,240 --> 00:36:26,280 It just feels a bit numb at the moment. 594 00:36:26,280 --> 00:36:28,320 Yeah, and that's quite normal, as well. All right? 595 00:36:30,360 --> 00:36:34,360 I didn't know whether I could do it or not, to tell you the truth. 596 00:36:35,560 --> 00:36:36,960 And I did it. 597 00:36:42,920 --> 00:36:46,280 Can you grip my fingers? Bryn? Bryn? 598 00:36:46,280 --> 00:36:50,240 Grip my fingers. Hard. Harder than that. 599 00:36:50,240 --> 00:36:51,880 Well done. Let go. 600 00:36:51,880 --> 00:36:54,720 Because he's had an operation on his brain, 601 00:36:54,720 --> 00:36:58,360 we need to make sure that his cognitive function 602 00:36:58,360 --> 00:37:00,320 is returning to normal, 603 00:37:00,320 --> 00:37:06,640 so we ask fairly standard questions just to see how aware he is. 604 00:37:06,640 --> 00:37:08,160 HE GROANS 605 00:37:09,560 --> 00:37:13,920 People say to me, "Are you nervous? Are you frightened?" I'm not. 606 00:37:13,920 --> 00:37:16,880 This chance doesn't come along to many people 607 00:37:16,880 --> 00:37:21,200 to be part of a trial that could truly shift medicine. 608 00:37:22,560 --> 00:37:26,000 Bryn Williams lives with his family in Glasgow. 609 00:37:26,000 --> 00:37:31,080 He was diagnosed with Parkinson's six years ago at the age of 36. 610 00:37:31,080 --> 00:37:32,280 Hold on. 611 00:37:34,120 --> 00:37:36,360 He still has a good quality of life... 612 00:37:37,400 --> 00:37:41,040 Sore foot. Sore foot. Bye-bye. Bye-bye. 613 00:37:41,040 --> 00:37:44,560 ..but today, paralysing cramps stop him from walking. 614 00:37:44,560 --> 00:37:45,880 See you later. 615 00:37:50,880 --> 00:37:54,840 I don't want to be encased in concrete, 616 00:37:54,840 --> 00:37:58,560 trembling away, unable to function, having to be cleaned 617 00:37:58,560 --> 00:38:00,720 and all that sort of carry-on. 618 00:38:00,720 --> 00:38:03,080 That will not happen. 619 00:38:03,080 --> 00:38:05,440 Whatever has to happen to stop that happening, 620 00:38:05,440 --> 00:38:07,000 my girls will not see me do that. 621 00:38:09,000 --> 00:38:10,880 Every fight I have with Parkinson's, 622 00:38:10,880 --> 00:38:14,360 I'm fighting it because I want to be there for my little girls 623 00:38:14,360 --> 00:38:17,000 and I want to walk them down the aisle 624 00:38:17,000 --> 00:38:19,200 and I want to deliver a speech at the wedding. 625 00:38:23,880 --> 00:38:26,520 After six hours in the operating theatre, 626 00:38:26,520 --> 00:38:29,120 Bryn's wife Vicky has come to see him. 627 00:38:29,120 --> 00:38:34,040 Hello. Hello. How are you? You've changed. 628 00:38:34,040 --> 00:38:36,320 SHE LAUGHS 629 00:38:36,320 --> 00:38:38,520 You haven't really. No. How have you been? 630 00:38:38,520 --> 00:38:41,960 I'm good. How are you? Ah, I'm OK. 631 00:38:41,960 --> 00:38:44,680 I was only out for two minutes. Were you?! Mm-hm. 632 00:38:44,680 --> 00:38:48,680 So, it's all a big farce? Yeah. Was it? 633 00:38:48,680 --> 00:38:51,400 Well, you've got a dirty big bandage on your head, so... 634 00:38:51,400 --> 00:38:54,520 Oh, no! SHE LAUGHS 635 00:38:56,600 --> 00:38:59,640 Nine of the 42 volunteers have had surgery, 636 00:38:59,640 --> 00:39:01,960 and all have gone smoothly so far. 637 00:39:03,680 --> 00:39:07,240 Soon, the drug infusions will begin 638 00:39:07,240 --> 00:39:09,880 with no-one knowing who's getting GDNF 639 00:39:09,880 --> 00:39:13,000 and who's receiving the placebo. 640 00:39:13,000 --> 00:39:17,880 But first, the skin needs to heal and seal around their new ports. 641 00:39:23,800 --> 00:39:29,600 Six weeks post-op and Tom's port must still be cleaned daily. 642 00:39:29,600 --> 00:39:34,040 INTERVIEWER: How sore is it, Tom? Erm, on a scale of one to ten, 643 00:39:34,040 --> 00:39:37,680 it's about 11, but I can take it. 644 00:39:37,680 --> 00:39:40,240 Yeah. You don't normally feel anything. 645 00:39:40,240 --> 00:39:43,120 I can't actually feel a thing. I'm just going to hold your head. 646 00:39:45,040 --> 00:39:47,440 It's a pity I don't have a bit more hair, really. 647 00:39:47,440 --> 00:39:50,080 You actually said you wanted me to get a toupee. 648 00:39:50,080 --> 00:39:52,040 We thought maybe just a piece of hair, 649 00:39:52,040 --> 00:39:55,040 like a well-done wig, that went around the hair, 650 00:39:55,040 --> 00:39:57,640 like, the bottom part, so it looked like your own hair. 651 00:39:57,640 --> 00:39:59,600 But I think your hair's going to grow over it 652 00:39:59,600 --> 00:40:01,800 cos it's already kind of coming down over it. 653 00:40:01,800 --> 00:40:04,240 So, as soon as the graft is all healed, 654 00:40:04,240 --> 00:40:06,200 I think you won't notice it, actually. 655 00:40:06,200 --> 00:40:08,000 I resisted the toupee idea. 656 00:40:08,000 --> 00:40:09,920 BOTH LAUGH 657 00:40:09,920 --> 00:40:13,720 Tom's scars are healing, but since the surgery, 658 00:40:13,720 --> 00:40:16,040 he's been struggling with his Parkinson's symptoms. 659 00:40:16,040 --> 00:40:18,280 The nights, I think, have been the worst bit. 660 00:40:18,280 --> 00:40:21,720 Isn't it, Tom? Yeah. Basically, you've had to get me out of bed. Mm. 661 00:40:21,720 --> 00:40:24,360 And I haven't been able to move in bed and... 662 00:40:24,360 --> 00:40:26,560 It's the first time I've felt like your carer... 663 00:40:26,560 --> 00:40:28,400 Sorry. For God's sake! 664 00:40:29,640 --> 00:40:31,880 ..not your wife. I've been your carer. 665 00:40:31,880 --> 00:40:35,080 It's just been really hard. Really hard. 666 00:40:35,080 --> 00:40:38,440 Cos I like to be your wife, not your carer. 667 00:40:38,440 --> 00:40:40,200 But anyway... 668 00:40:40,200 --> 00:40:42,440 SHE LAUGHS 669 00:40:45,720 --> 00:40:47,640 Yeah, that must be quite tough, actually. 670 00:40:53,960 --> 00:40:55,960 The infusions are prepared to order 671 00:40:55,960 --> 00:40:58,920 in sterile conditions in the hospital's pharmacy. 672 00:41:00,360 --> 00:41:03,160 Volunteers have been randomised by a computer 673 00:41:03,160 --> 00:41:06,080 to receive either GDNF or a placebo fluid... 674 00:41:07,440 --> 00:41:11,320 ..and only one person knows who'll be receiving what. 675 00:41:11,320 --> 00:41:14,480 Clearly, the pharmacist has to know what they're putting in the tubing, 676 00:41:14,480 --> 00:41:16,120 so the pharmacist knows. 677 00:41:16,120 --> 00:41:17,880 But outside of the pharmacy, 678 00:41:17,880 --> 00:41:21,520 the staff giving the drug and the patients are blinded. 679 00:41:21,520 --> 00:41:24,240 They don't know whether they're having the active drug 680 00:41:24,240 --> 00:41:25,480 or the placebo. 681 00:41:33,400 --> 00:41:35,960 It's March 2013. 682 00:41:35,960 --> 00:41:38,080 We thought if we sat you in that chair... 683 00:41:38,080 --> 00:41:42,560 It's taken three months for the skin around Tom's port to heal. 684 00:41:42,560 --> 00:41:44,800 So, I'm going to start by cleaning the port. 685 00:41:44,800 --> 00:41:48,200 Today, the port will be opened for the first of ten monthly infusions 686 00:41:48,200 --> 00:41:50,680 of either GDNF or placebo. 687 00:41:52,880 --> 00:41:55,440 Each infusion will take two hours. 688 00:41:57,400 --> 00:41:59,320 The volunteers will stay on their normal 689 00:41:59,320 --> 00:42:01,440 Parkinson's medication throughout 690 00:42:01,440 --> 00:42:03,680 as they couldn't function without it. 691 00:42:03,680 --> 00:42:06,200 Fingers crossed for me, people. 692 00:42:06,200 --> 00:42:08,120 Yeah, it's a huge day. 693 00:42:09,360 --> 00:42:12,680 OK. So, I'm just going to hold your head slightly firmly 694 00:42:12,680 --> 00:42:14,600 just to prop that on, OK? 695 00:42:15,800 --> 00:42:18,480 This week, we got quite upbeat, actually. 696 00:42:18,480 --> 00:42:20,560 I think we both did. Yeah? 697 00:42:20,560 --> 00:42:24,600 Certainly, I've been feeling really positive that this is it now. 698 00:42:24,600 --> 00:42:27,440 Hopefully, it's GDNF. DOCTOR: That's right. Well done. 699 00:42:27,440 --> 00:42:29,640 I'm just going to pop in the applications. 700 00:42:34,040 --> 00:42:37,080 MACHINE BEEPS That's in. 701 00:42:37,080 --> 00:42:38,800 Very well done. 702 00:42:42,720 --> 00:42:44,840 Very good. Good. And relax. 703 00:42:44,840 --> 00:42:47,560 THEY LAUGH 704 00:42:50,040 --> 00:42:52,720 It works! You can go now. HE LAUGHS 705 00:42:52,720 --> 00:42:54,480 For everyone... I can retire! 706 00:42:54,480 --> 00:42:57,000 ..the first few infusions go without a hitch. 707 00:42:59,560 --> 00:43:02,560 Yes, but it was that thing, wasn't it? That thing, yeah. 708 00:43:02,560 --> 00:43:04,040 And it was across there 709 00:43:04,040 --> 00:43:06,320 and we felt like we were being interrogated. 710 00:43:06,320 --> 00:43:10,240 Inevitably, speculation begins about who's on the drug 711 00:43:10,240 --> 00:43:12,040 and who's on the placebo. 712 00:43:12,040 --> 00:43:14,480 Oh, I do so hope he doesn't have the placebo. 713 00:43:14,480 --> 00:43:19,240 I think that's a cruel, cruel thing to have a huge operation like that 714 00:43:19,240 --> 00:43:22,000 and then have to have a placebo. 715 00:43:22,000 --> 00:43:24,800 Is that human? Not really, is it? 716 00:43:26,960 --> 00:43:29,400 Simply the effect of going to see the doctor 717 00:43:29,400 --> 00:43:31,560 may begin to make you feel better, 718 00:43:31,560 --> 00:43:35,080 particularly if the patient has some sense or hope 719 00:43:35,080 --> 00:43:37,120 that that's going to be the case. 720 00:43:37,120 --> 00:43:40,080 And on the whole, the more you're doing to patients, 721 00:43:40,080 --> 00:43:42,160 the more they may anticipate benefit. 722 00:43:42,160 --> 00:43:45,000 Have you ever seen him down? TOM'S WIFE: Probably once or twice. 723 00:43:46,480 --> 00:43:48,760 So, if you're putting them forward for brain surgery 724 00:43:48,760 --> 00:43:50,480 and then putting a port behind their ear 725 00:43:50,480 --> 00:43:52,160 and then infusing them every four weeks, 726 00:43:52,160 --> 00:43:56,160 the levels of anticipation may be pretty high at that stage. 727 00:43:56,160 --> 00:44:00,080 Steve's original study didn't have a placebo group, 728 00:44:00,080 --> 00:44:03,520 leaving it vulnerable to claims that it was belief in the treatment 729 00:44:03,520 --> 00:44:07,800 rather than a true biological effect that led to improvements. 730 00:44:07,800 --> 00:44:10,200 The patients look heaps better. 731 00:44:10,200 --> 00:44:12,280 That said, I do genuinely believe 732 00:44:12,280 --> 00:44:17,200 that that level of response could have been a placebo effect. 733 00:44:17,200 --> 00:44:21,000 And so, although it may seem cruel to put people through brain surgery 734 00:44:21,000 --> 00:44:24,760 and then have half of them have to have dummy, 735 00:44:24,760 --> 00:44:27,080 there isn't really another way of deciding 736 00:44:27,080 --> 00:44:32,560 if one is genuinely better than simply giving distilled water. 737 00:44:38,800 --> 00:44:42,520 The volunteers settle into a rhythm of monthly hospital visits, 738 00:44:42,520 --> 00:44:45,000 infusions and endless assessments. 739 00:44:45,000 --> 00:44:46,800 I'm going to shine a light in your eye. 740 00:44:51,680 --> 00:44:55,160 Everything is documented, from minor colds and headaches 741 00:44:55,160 --> 00:44:58,200 to changes in sleep patterns or mood. 742 00:44:58,200 --> 00:45:00,600 Do you want to do it at the present time, as well? 743 00:45:00,600 --> 00:45:02,960 Well, the present time would be the same. Yeah. 744 00:45:03,920 --> 00:45:05,240 Good at that. 745 00:45:08,320 --> 00:45:12,480 The scale of the record-keeping is somewhat mind-blowing. 746 00:45:15,240 --> 00:45:18,480 You end up with a room full of documentation, 747 00:45:18,480 --> 00:45:21,920 and it's literally thousands and thousands of pieces of data. 748 00:45:36,080 --> 00:45:38,720 Nine months since the start of the trial, 749 00:45:38,720 --> 00:45:45,040 and after six infusions, Tom can run without any medication. 750 00:45:45,040 --> 00:45:47,920 Feels like fluid again. 751 00:45:47,920 --> 00:45:52,600 It feels like a pharmaceutically manufactured version of me. 752 00:45:52,600 --> 00:45:54,240 Feels like the real me. 753 00:45:54,240 --> 00:45:58,480 Yeah, I do think it's new. It's really exciting. 754 00:45:58,480 --> 00:45:59,920 Tom's sleeping longer. 755 00:45:59,920 --> 00:46:02,960 He's not requiring me to get him out of bed at night-time any more, 756 00:46:02,960 --> 00:46:05,720 which he was requiring up until about a month ago. 757 00:46:05,720 --> 00:46:06,920 Go on, get it! 758 00:46:09,120 --> 00:46:11,080 And it's little things in the morning, 759 00:46:11,080 --> 00:46:14,600 like he can move his hands, so that's really positive. 760 00:46:18,640 --> 00:46:21,680 There are signs that others might be improving, too. 761 00:46:26,520 --> 00:46:28,360 It'll be amazing - amazing - 762 00:46:28,360 --> 00:46:31,000 to just have that freedom of choice, to... 763 00:46:32,200 --> 00:46:35,920 ..not be contained by it, cos it contains you. 764 00:46:48,240 --> 00:46:51,200 It's December 2013, 765 00:46:51,200 --> 00:46:53,360 and Chris Brownbill returns to the hospital 766 00:46:53,360 --> 00:46:55,440 for an infusion and MRI scan. 767 00:46:56,560 --> 00:46:59,240 During the scan, he feels unwell. 768 00:46:59,240 --> 00:47:01,680 He makes it back to the clinic room afterwards, 769 00:47:01,680 --> 00:47:04,520 but the medical team can tell that something is wrong. 770 00:47:07,760 --> 00:47:10,000 Do you want to go through and take a seat? 771 00:47:10,000 --> 00:47:12,440 What was immediately obvious, as he came through the door, 772 00:47:12,440 --> 00:47:14,480 was that one side of his face was drooping. 773 00:47:14,480 --> 00:47:18,960 Immediately, Chris undergoes an urgent neurological examination. 774 00:47:18,960 --> 00:47:24,840 Here, we have an MRI scan cut across the brain like this, 775 00:47:24,840 --> 00:47:28,320 and here, these little black holes are the tubes or catheters, 776 00:47:28,320 --> 00:47:30,720 and what you're seeing around this back catheter 777 00:47:30,720 --> 00:47:32,160 is this bright area, 778 00:47:32,160 --> 00:47:35,640 which is suggestive of a stroke having occurred. 779 00:47:38,840 --> 00:47:40,880 Chris recovers. 780 00:47:41,880 --> 00:47:43,720 Well, I'm a lot better than I was. 781 00:47:43,720 --> 00:47:47,160 I was quite a mess, really, both emotionally and physically. 782 00:47:47,160 --> 00:47:49,480 So, it's a big improvement, 783 00:47:49,480 --> 00:47:52,040 and that's why I'm feeling better within myself 784 00:47:52,040 --> 00:47:54,480 because I can feel myself coming back 785 00:47:54,480 --> 00:47:57,960 from quite a dark place, really. 786 00:47:57,960 --> 00:48:02,360 Suddenly, there's a great unknown that puts the whole project at risk. 787 00:48:05,120 --> 00:48:07,080 To date, we've only given 788 00:48:07,080 --> 00:48:09,280 a relatively small number of infusions 789 00:48:09,280 --> 00:48:10,960 compared with the more than 1,000 790 00:48:10,960 --> 00:48:13,160 that are going to be given by the end of the study. 791 00:48:13,160 --> 00:48:15,200 And so we just don't know whether this is something 792 00:48:15,200 --> 00:48:18,240 we're going to keep seeing or whether it's a freak and a one-off. 793 00:48:20,040 --> 00:48:23,040 And then another disaster. 794 00:48:24,360 --> 00:48:28,200 Lying in bed, I rolled over onto my left side and the... 795 00:48:29,200 --> 00:48:32,680 ..port came loose. 796 00:48:35,480 --> 00:48:37,640 I heard a crack in my ear. 797 00:48:39,840 --> 00:48:42,240 Bryn becomes the first of five patients 798 00:48:42,240 --> 00:48:45,280 whose ports fail to bond with the bone. 799 00:48:45,280 --> 00:48:47,400 To create a seal around the base of the port, 800 00:48:47,400 --> 00:48:50,560 it needs to be immobile. As soon as it starts moving, 801 00:48:50,560 --> 00:48:54,280 then the skin's going to be breaking away from the port. 802 00:48:54,280 --> 00:48:56,600 Then infection can travel along all the tubing 803 00:48:56,600 --> 00:48:58,080 and get into the brain, 804 00:48:58,080 --> 00:49:01,680 and that would be potentially a life-threatening problem. 805 00:49:06,400 --> 00:49:09,640 Steve heads back to the engineers in Gloucestershire 806 00:49:09,640 --> 00:49:12,640 to try and find a fix as fast as possible. 807 00:49:15,520 --> 00:49:17,880 The wobbly ports and Chris's stroke 808 00:49:17,880 --> 00:49:20,920 are what are known as serious adverse events. 809 00:49:22,040 --> 00:49:25,880 They trigger the involvement of an independent off-site committee 810 00:49:25,880 --> 00:49:28,720 whose primary concern is patient safety. 811 00:49:29,960 --> 00:49:34,280 15 months since the start, the trial is stopped. 812 00:49:35,840 --> 00:49:39,720 We have to understand, before we put this into anyone else, 813 00:49:39,720 --> 00:49:41,320 why these events have occurred 814 00:49:41,320 --> 00:49:43,960 and if it's safe and reasonable to carry on. 815 00:49:47,040 --> 00:49:49,480 If the trial doesn't get going again, 816 00:49:49,480 --> 00:49:52,000 the patients will have to go through further surgery 817 00:49:52,000 --> 00:49:54,560 to remove their ports. 818 00:49:54,560 --> 00:49:57,520 We could go to the seaside. And what else could we do? 819 00:49:58,800 --> 00:50:02,800 This is the reality of certain clinical trials 820 00:50:02,800 --> 00:50:07,120 that carry significant risks - that you may not get to the end. 821 00:50:07,120 --> 00:50:09,760 And people have to understand that at the beginning. 822 00:50:11,560 --> 00:50:14,240 Chris Brownbill's port is taken out. 823 00:50:15,480 --> 00:50:18,120 It's too risky for him to continue... 824 00:50:18,120 --> 00:50:22,440 That's healed nice, hasn't it? Yeah, the port site. Really nice. 825 00:50:22,440 --> 00:50:24,360 ..and he is taken off the trial. 826 00:50:27,400 --> 00:50:29,240 I just read the happy script. 827 00:50:29,240 --> 00:50:31,720 I expected to go for the trial, 828 00:50:31,720 --> 00:50:35,160 get the GDNF, improve. That was my scenario. 829 00:50:35,160 --> 00:50:37,120 I didn't see any other scenario than that. 830 00:50:38,600 --> 00:50:41,880 Parkinson's - it's something that you know you're going to get worse 831 00:50:41,880 --> 00:50:45,480 so your natural instinct is to face it. 832 00:50:45,480 --> 00:50:49,760 There's nothing going to stop me trying to get rid of this condition. 833 00:50:49,760 --> 00:50:54,240 But after today, I hope that we can just perhaps 834 00:50:54,240 --> 00:50:56,440 get on with our lives a little bit. 835 00:51:00,240 --> 00:51:01,800 Yeah. 836 00:51:04,800 --> 00:51:07,120 Following weeks of discussion 837 00:51:07,120 --> 00:51:10,280 and with no other incidents during an infusion, 838 00:51:10,280 --> 00:51:13,720 the independent monitors conclude that Chris's stroke 839 00:51:13,720 --> 00:51:15,600 is probably a one-off 840 00:51:15,600 --> 00:51:18,600 and decide it's safe to restart the trial. 841 00:51:19,920 --> 00:51:23,680 And the engineers have devised a fix for the wobbly ports. 842 00:51:23,680 --> 00:51:25,480 Can you push me? 843 00:51:25,480 --> 00:51:28,160 It means more surgery for Bryn. 844 00:51:29,160 --> 00:51:30,640 A year ago this week, 845 00:51:30,640 --> 00:51:33,440 Ella decided she wanted to go to see One Direction, 846 00:51:33,440 --> 00:51:35,200 and she made me buy tickets. 847 00:51:35,200 --> 00:51:38,120 I was going to have to go to One Direction tonight in Edinburgh. 848 00:51:39,960 --> 00:51:44,800 I hate them. They're a racket. Just noise. Talentless gimps. 849 00:51:46,080 --> 00:51:48,240 And I've got out of it cos of this trial... 850 00:51:49,640 --> 00:51:51,720 ..and she'll never, ever speak to me again. 851 00:51:51,720 --> 00:51:54,360 But you know what? It's worth it. 852 00:52:04,120 --> 00:52:06,800 Well, you can see it's quite wobbly, that port. 853 00:52:09,120 --> 00:52:13,480 Our rescue device is a cylinder into which the old port sits. 854 00:52:13,480 --> 00:52:15,120 OK. 855 00:52:15,120 --> 00:52:16,480 Oh! 856 00:52:17,800 --> 00:52:21,400 The cylinder has stabilisers that are anchored into the bone 857 00:52:21,400 --> 00:52:24,040 so that the port can't move. 858 00:52:25,880 --> 00:52:29,360 HE GROANS Nice, deep breaths, Bryn. 859 00:52:29,360 --> 00:52:34,600 The way of fixing the port in is much more robust. 860 00:52:34,600 --> 00:52:36,960 It'll probably go on changing a bit more. 861 00:52:36,960 --> 00:52:38,680 It's just unfortunate there are people 862 00:52:38,680 --> 00:52:40,480 who have to go through all they have, 863 00:52:40,480 --> 00:52:44,160 as well as going through their suffering at the other end. 864 00:52:44,160 --> 00:52:45,560 Morning. Morning. 865 00:52:45,560 --> 00:52:47,600 After an eight-month hiatus, 866 00:52:47,600 --> 00:52:49,840 the trial can now get back under way. 867 00:52:49,840 --> 00:52:51,680 So, that's hopefully good news, 868 00:52:51,680 --> 00:52:56,240 but obviously, I'm aware that things could still go wrong along the way. 869 00:52:56,240 --> 00:52:58,000 Take a seat through to our waiting room. 870 00:52:58,000 --> 00:52:59,800 It's just round here on the right-hand side. 871 00:52:59,800 --> 00:53:01,480 Right, thank you. Cheers. 872 00:53:01,480 --> 00:53:04,240 Somewhere in Southmead Hospital, 873 00:53:04,240 --> 00:53:07,200 there's a vial with a liquid in it 874 00:53:07,200 --> 00:53:09,480 which is going to go into my brain today. 875 00:53:12,120 --> 00:53:14,760 If it works, I'll be a dad for the rest of my life. 876 00:53:14,760 --> 00:53:17,640 If it doesn't work, I'll not be a dad worth having. 877 00:53:32,280 --> 00:53:34,560 Metal. Yeah. To go at the end. 878 00:53:34,560 --> 00:53:36,760 With the trial back on track, 879 00:53:36,760 --> 00:53:40,400 the guessing game about who is and isn't getting the real drug 880 00:53:40,400 --> 00:53:42,080 begins in earnest. 881 00:53:42,080 --> 00:53:44,640 Look how well the trees are doing. 882 00:53:44,640 --> 00:53:48,080 They've got so big. Lean this against that. 883 00:53:48,080 --> 00:53:49,960 Pass me the hammer a minute. 884 00:53:49,960 --> 00:53:52,400 Yeah, last night, it took me about 15 minutes 885 00:53:52,400 --> 00:53:54,840 to unbutton my shirt when I got home. 886 00:53:54,840 --> 00:53:57,480 Oh, there it is. There it is. 887 00:53:57,480 --> 00:53:59,360 After five infusions, 888 00:53:59,360 --> 00:54:01,920 Nick is convinced he's on the placebo. 889 00:54:04,080 --> 00:54:07,040 His last assessment reveals no improvement 890 00:54:07,040 --> 00:54:08,840 since he started the trial. 891 00:54:14,640 --> 00:54:15,960 I'm hopeful. 892 00:54:17,400 --> 00:54:21,800 I don't know. Sometimes, I think I'm clutching at straws, 893 00:54:21,800 --> 00:54:24,720 but at the other end of the scale, 894 00:54:24,720 --> 00:54:28,040 Bristol Southmead and all these people 895 00:54:28,040 --> 00:54:30,760 wouldn't have thrown three million quid at this project. 896 00:54:30,760 --> 00:54:33,200 They've done their homework. 897 00:54:33,200 --> 00:54:35,480 Watch the little stream. 898 00:54:35,480 --> 00:54:38,320 Can we drink the water? Mm, I wouldn't. 899 00:54:38,320 --> 00:54:41,920 Why? Well, cos sometimes there's badger poo in it. 900 00:54:45,800 --> 00:54:49,040 Ron Johnson has also had five infusions. 901 00:54:50,120 --> 00:54:53,560 His tremors seem to have gotten worse. 902 00:54:53,560 --> 00:54:59,440 And also he was very sharp-minded, you know, whereas now it's very... 903 00:55:00,520 --> 00:55:04,880 ..slow and sometimes quite confused. 904 00:55:06,800 --> 00:55:09,600 If this is as good as it gets, 905 00:55:09,600 --> 00:55:14,640 if the ultimate is what I'm going through every day... 906 00:55:15,800 --> 00:55:17,480 ..I'd be pissed off. 907 00:55:20,960 --> 00:55:26,200 In Cornwall, Kaye is convinced her infusions are working. 908 00:55:29,440 --> 00:55:32,320 The first thing that happened was I could smell. 909 00:55:32,320 --> 00:55:33,960 I've started to get my smell back. 910 00:55:33,960 --> 00:55:35,880 I can smell all kinds of subtleties now. 911 00:55:35,880 --> 00:55:38,240 But the first thing that I smelled was my dog 912 00:55:38,240 --> 00:55:40,240 who was... 913 00:55:41,440 --> 00:55:45,160 He broke wind and I'm like, "Oh, what on Earth is that?" 914 00:55:45,160 --> 00:55:47,760 My mum was there and she said, "What?" 915 00:55:47,760 --> 00:55:50,440 I said, "What was that smell?" She said, "You can't smell." 916 00:55:50,440 --> 00:55:52,640 I said, "I certainly smelled that." 917 00:55:56,480 --> 00:55:58,600 Bryn also notices a difference. 918 00:56:01,160 --> 00:56:03,200 Our problem was writing clearly. 919 00:56:03,200 --> 00:56:05,880 Other patients are reporting improvements, too. 920 00:56:07,040 --> 00:56:09,440 Some of the patients do seem to be getting better, 921 00:56:09,440 --> 00:56:13,160 and whilst that's encouraging, I'm also very aware 922 00:56:13,160 --> 00:56:16,240 that it could be a placebo-type response. 923 00:56:16,240 --> 00:56:19,640 Nevertheless, if nobody seemed to be doing anything, 924 00:56:19,640 --> 00:56:21,840 then the chances of seeing a difference, of course, 925 00:56:21,840 --> 00:56:23,680 would be much lower. 926 00:56:23,680 --> 00:56:27,480 In September 2014, almost two years 927 00:56:27,480 --> 00:56:29,280 since the start of the trial, 928 00:56:29,280 --> 00:56:32,000 the biggest pharmaceutical company in the world 929 00:56:32,000 --> 00:56:36,720 decides to invest in GDNF and the Bristol delivery system. 930 00:56:36,720 --> 00:56:39,760 They're taking an option out early, that if it is positive, 931 00:56:39,760 --> 00:56:42,040 they've got first dibs on going forward 932 00:56:42,040 --> 00:56:44,640 into a Phase 3 study. 933 00:56:44,640 --> 00:56:46,880 Because of the costs of those Phase 3 studies, 934 00:56:46,880 --> 00:56:49,920 even if we're successful and we show the drug works, 935 00:56:49,920 --> 00:56:52,880 without that backing, it wouldn't go forward anyway, 936 00:56:52,880 --> 00:56:56,000 so it makes the whole thing more meaningful. 937 00:56:56,000 --> 00:56:57,640 That's about as good as it gets. 938 00:56:57,640 --> 00:57:00,520 You know, this is the biggest drug company in the world. 939 00:57:00,520 --> 00:57:03,040 They have all the resources, and if they are keen 940 00:57:03,040 --> 00:57:06,040 to take a completely novel form of therapy forward, 941 00:57:06,040 --> 00:57:07,920 that's a major advance. 942 00:57:10,400 --> 00:57:12,640 The stakes are high. 943 00:57:12,640 --> 00:57:15,800 The scientific community is watching. 944 00:57:15,800 --> 00:57:20,000 More than ever, everything depends on the outcome of the trial. 945 00:57:20,000 --> 00:57:23,400 Got to say, I feel great. 946 00:57:23,400 --> 00:57:26,920 I feel really good. 947 00:57:26,920 --> 00:57:29,920 Still as you like. 948 00:57:29,920 --> 00:57:31,560 Come on! 949 00:57:32,600 --> 00:57:36,200 Yes! Yes! 950 00:57:36,200 --> 00:57:39,320 The trial is now almost at the halfway mark, 951 00:57:39,320 --> 00:57:42,160 with the future of millions of people worldwide 952 00:57:42,160 --> 00:57:44,960 resting on what happens next. 953 00:57:44,960 --> 00:57:46,600 Yes! 954 00:57:50,320 --> 00:57:53,240 Next time, the trial enters its second phase, 955 00:57:53,240 --> 00:57:55,920 and everyone receives the GDNF drug. 956 00:57:55,920 --> 00:57:58,200 I'm going to get this stuff. 957 00:57:58,200 --> 00:58:01,440 There are extraordinary transformations. 958 00:58:01,440 --> 00:58:03,120 It was like a bloody miracle. 959 00:58:03,120 --> 00:58:05,280 Look at my hands. You know, they're just... 960 00:58:05,280 --> 00:58:06,720 Look at that. 961 00:58:06,720 --> 00:58:09,320 But there is desperation, too. HE GROANS 962 00:58:09,320 --> 00:58:11,520 I thought I was going to die. 963 00:58:11,520 --> 00:58:14,000 Finally, after five years... 964 00:58:14,000 --> 00:58:15,440 So, here we go, eh? 965 00:58:15,440 --> 00:58:17,680 ..we find out if the drug works 966 00:58:17,680 --> 00:58:21,920 and if GDNF is the breakthrough the world has been waiting for. 967 00:58:57,220 --> 00:59:00,260 This programme contains some strong language 968 00:59:00,260 --> 00:59:01,940 No qualms about going ahead? Too late now! 969 00:59:01,940 --> 00:59:06,620 In 2012, a remarkable medical trial began in Bristol. 970 00:59:06,620 --> 00:59:08,340 And I'll see you tomorrow. 971 00:59:08,340 --> 00:59:11,020 42 volunteers have had surgery 972 00:59:11,020 --> 00:59:14,460 to implant a titanium port in their skulls... 973 00:59:14,460 --> 00:59:16,700 So, we're going right posterior. 974 00:59:16,700 --> 00:59:19,780 ..to deliver a new drug deep into their brains. 975 00:59:19,780 --> 00:59:22,180 Going to drive the needles in, OK? That's fine. 976 00:59:22,180 --> 00:59:25,060 The hope is that it will reverse Parkinson's - 977 00:59:25,060 --> 00:59:29,180 the world's second most common neurodegenerative disorder. 978 00:59:29,180 --> 00:59:30,940 We could do great harm here 979 00:59:30,940 --> 00:59:34,220 and we could genuinely make people worse than they are 980 00:59:34,220 --> 00:59:35,580 before they started. 981 00:59:37,020 --> 00:59:40,260 It's a double blind, placebo control trial... 982 00:59:40,260 --> 00:59:42,100 Screw your eyes up really tight. 983 00:59:42,100 --> 00:59:45,380 ..which means for nine months, half have been getting the real drug 984 00:59:45,380 --> 00:59:46,780 and half a dummy drug. 985 00:59:46,780 --> 00:59:48,700 I'm going to put the needles in. 986 00:59:48,700 --> 00:59:50,340 Now at the halfway point, 987 00:59:50,340 --> 00:59:53,180 all the volunteers start to receive the real drug... 988 00:59:53,180 --> 00:59:54,900 I'm going to get this stuff. 989 00:59:54,900 --> 00:59:56,740 ..for the next nine months. 990 00:59:56,740 --> 01:00:01,500 It didn't seem ethical to put people through having brain surgery, 991 01:00:01,500 --> 01:00:03,180 having the device inserted, 992 01:00:03,180 --> 01:00:05,460 without ever having the prospect of the drug. 993 01:00:07,100 --> 01:00:10,340 For some, there are remarkable transformations... 994 01:00:11,780 --> 01:00:14,020 The more I'm doing it, the more I'm smiling. 995 01:00:14,020 --> 01:00:17,460 I'm thinking, "This ain't real. This ain't real." 996 01:00:17,460 --> 01:00:19,420 And now he's back! 997 01:00:20,700 --> 01:00:23,340 For others, disappointment and setback. 998 01:00:23,340 --> 01:00:26,580 I felt something as I went in. It was felt like a vessel. 999 01:00:26,580 --> 01:00:28,260 Shoot. 1000 01:00:28,260 --> 01:00:31,420 Lying there, I thought I was going to die. 1001 01:00:31,420 --> 01:00:32,900 Finally... 1002 01:00:32,900 --> 01:00:34,500 So, here we go, eh? 1003 01:00:34,500 --> 01:00:37,620 ..after five years, we find out if the drug works... 1004 01:00:37,620 --> 01:00:43,180 We needed to see a 20% difference between the treated group 1005 01:00:43,180 --> 01:00:45,300 with GDNF versus the placebo group. 1006 01:00:45,300 --> 01:00:49,460 ..and if GDNF is the breakthrough the world has been waiting for. 1007 01:00:56,780 --> 01:00:58,860 Right, and back. 1008 01:01:01,380 --> 01:01:03,700 The amazing thing to me is in my hands. 1009 01:01:03,700 --> 01:01:05,340 See? No tremor. 1010 01:01:06,620 --> 01:01:07,980 Well, very little tremor. 1011 01:01:07,980 --> 01:01:10,020 This is my hand that usually tremors a lot. 1012 01:01:11,580 --> 01:01:13,540 My smile's coming back. 1013 01:01:13,540 --> 01:01:15,540 I can taste things better. 1014 01:01:15,540 --> 01:01:18,740 I can go for a whole day without having a nap. 1015 01:01:20,420 --> 01:01:22,860 It might not seem much to you but it's a lot to me. 1016 01:01:24,420 --> 01:01:26,700 It's summer 2015 - 1017 01:01:26,700 --> 01:01:31,900 two and a half years since 42 men and women from across the UK 1018 01:01:31,900 --> 01:01:35,460 signed up for one of the most extraordinary clinical trials 1019 01:01:35,460 --> 01:01:37,660 the world has ever seen. 1020 01:01:37,660 --> 01:01:39,540 Going to drive the needles in, OK? 1021 01:01:39,540 --> 01:01:42,940 They're helping to test a new drug called GDNF 1022 01:01:42,940 --> 01:01:46,540 that could be the first to reverse Parkinson's - 1023 01:01:46,540 --> 01:01:50,260 a movement disorder one in 39 of us is destined to get. 1024 01:01:53,740 --> 01:01:58,700 The trial is now at the halfway point and the picture is mixed. 1025 01:02:01,540 --> 01:02:04,900 I hope to God that I am on the placebo. 1026 01:02:04,900 --> 01:02:11,780 Because...so far, I don't feel any real difference. 1027 01:02:14,460 --> 01:02:20,380 Just feeling crap and disabled, and non-functioning, 1028 01:02:20,380 --> 01:02:22,780 and I hate it. 1029 01:02:27,940 --> 01:02:30,700 I think it's certainly the case that we're not seeing people 1030 01:02:30,700 --> 01:02:33,140 turning up and saying, "I've thrown away my tablets." 1031 01:02:33,140 --> 01:02:37,660 So we're not seeing that magnitude of benefit or change. 1032 01:02:39,420 --> 01:02:42,260 But there seems to be enough improvement in some 1033 01:02:42,260 --> 01:02:45,300 that there may be a significant difference between the two groups. 1034 01:02:45,300 --> 01:02:46,300 Blimey! 1035 01:02:51,580 --> 01:02:53,260 For the past nine months, 1036 01:02:53,260 --> 01:02:56,300 the volunteers have been having monthly infusions 1037 01:02:56,300 --> 01:02:58,860 through a port implanted into their head 1038 01:02:58,860 --> 01:03:01,580 at the start of the trial. 1039 01:03:01,580 --> 01:03:03,980 Every two months, they are filmed 1040 01:03:03,980 --> 01:03:06,420 attempting a series of movement tasks 1041 01:03:06,420 --> 01:03:09,260 to see if they've improved. 1042 01:03:09,260 --> 01:03:10,740 Smile at the camera. 1043 01:03:10,740 --> 01:03:12,540 Screw your eyes up really tight. 1044 01:03:12,540 --> 01:03:17,180 So far, no-one knows if they're getting the real drug or a placebo. 1045 01:03:18,500 --> 01:03:21,660 Now, everything's about to change. 1046 01:03:21,660 --> 01:03:26,340 So we're now at the end of the first nine months where patients, 1047 01:03:26,340 --> 01:03:29,620 both on the placebo and the GDNF, move over, 1048 01:03:29,620 --> 01:03:33,620 so that everybody receives active drug for the next nine months. 1049 01:03:36,260 --> 01:03:37,500 DOG BARKS 1050 01:03:38,940 --> 01:03:42,780 In the first few months of the trial, Tom Isaacs was convinced 1051 01:03:42,780 --> 01:03:45,780 he was on the real drug and getting better. 1052 01:03:48,020 --> 01:03:51,140 Now, he thinks he's been on the placebo. 1053 01:03:51,140 --> 01:03:53,940 Do you know what? I hope he's not on the drug... 1054 01:03:55,020 --> 01:03:58,260 ..because... It's worse. Yeah. Made me worse. 1055 01:03:58,260 --> 01:03:59,580 ..it's made him worse. 1056 01:03:59,580 --> 01:04:02,780 Compared to this time last year before for the surgery, 1057 01:04:02,780 --> 01:04:07,180 I'd say I'm 20% to 30% worse than I was at that time. 1058 01:04:09,020 --> 01:04:11,020 Really, really, it's been the year from hell. 1059 01:04:16,140 --> 01:04:18,900 The assessments, where the volunteers are taken off 1060 01:04:18,900 --> 01:04:22,380 their regular meds, to expose their baseline Parkinson's... 1061 01:04:22,380 --> 01:04:23,660 Go. 1062 01:04:23,660 --> 01:04:27,500 ..capture the change in Tom since the start of the trial. 1063 01:04:27,500 --> 01:04:28,620 That's it, Tom. 1064 01:04:28,620 --> 01:04:32,380 You want to go down or do you want...? Yeah. Go down. Yeah. 1065 01:04:34,540 --> 01:04:35,780 And again. 1066 01:04:35,780 --> 01:04:38,260 INTERVIEWER: If you could wind back the clock 12 months, 1067 01:04:38,260 --> 01:04:41,860 would you still embark on this trial? Yes. Of course. 1068 01:04:45,580 --> 01:04:48,740 Yes. Yes. It's a no-brainer, that one, isn't it? 1069 01:04:55,860 --> 01:04:58,820 In Parkinson's disease, there's a disconnect 1070 01:04:58,820 --> 01:05:01,340 between your decision to do something 1071 01:05:01,340 --> 01:05:03,860 and your ability to do it, 1072 01:05:03,860 --> 01:05:06,660 so you can't actually drive your motor system. 1073 01:05:06,660 --> 01:05:10,780 And it's down to a progressive loss of nerve cells - 1074 01:05:10,780 --> 01:05:13,980 they're involved in planning and executing movements. 1075 01:05:18,260 --> 01:05:21,180 The drugs currently available for Parkinson's work well 1076 01:05:21,180 --> 01:05:22,580 in the early years... 1077 01:05:24,060 --> 01:05:27,220 ..but over time they become less effective... 1078 01:05:29,260 --> 01:05:32,540 ..and they eventually cause serious side effects... 1079 01:05:32,540 --> 01:05:34,740 If I can get it on me... 1080 01:05:34,740 --> 01:05:38,620 ..including uncontrollable movement called dyskinesia. 1081 01:05:41,060 --> 01:05:44,860 For Jeff Tottle, a maintenance man and gardener from Somerset... 1082 01:05:47,620 --> 01:05:50,420 ..it makes earning a living very difficult. 1083 01:05:56,780 --> 01:06:00,540 Jeff is now at the end of the first half of the trial. 1084 01:06:00,540 --> 01:06:02,940 I honestly think I'm on the placebo... 1085 01:06:04,100 --> 01:06:06,300 ..cos I'm no different whatsoever. 1086 01:06:16,580 --> 01:06:19,020 As the disease progresses, nothing really touches 1087 01:06:19,020 --> 01:06:21,260 some of the key symptoms of Parkinson's disease... 1088 01:06:23,540 --> 01:06:26,820 ..and this is what ultimately has a major impact 1089 01:06:26,820 --> 01:06:28,500 on people's quality of life. 1090 01:06:28,500 --> 01:06:32,220 INTERVIEWER: Do you allow yourself to think about the future 1091 01:06:32,220 --> 01:06:33,420 if it doesn't work? 1092 01:06:33,420 --> 01:06:34,580 No. 1093 01:06:35,900 --> 01:06:37,860 I don't go as far down the road as that. 1094 01:06:41,060 --> 01:06:43,340 For the volunteers who think they've been on placebo 1095 01:06:43,340 --> 01:06:45,580 during the first half of the trial, 1096 01:06:45,580 --> 01:06:48,820 the start of the second nine months offers fresh hope. 1097 01:06:48,820 --> 01:06:49,860 Is it? 1098 01:06:51,220 --> 01:06:55,260 I'm going to get the stuff, I'm going to get better... 1099 01:06:56,340 --> 01:06:59,540 ..and everything's going to be rosy 1100 01:06:59,540 --> 01:07:02,460 and I might even buy my wife some flowers. Woohoo! 1101 01:07:04,140 --> 01:07:06,140 It doesn't get much better than that. 1102 01:07:06,140 --> 01:07:10,620 Hello. Hiya. Hello. How are you? How are you? Are you well? 1103 01:07:10,620 --> 01:07:14,060 It's my first definite infusion of real thing. 1104 01:07:14,060 --> 01:07:19,700 Are you nervous? Mmm. Yes. Are you? Well, no. 1105 01:07:19,700 --> 01:07:24,260 Father-of-two Bryn Williams is also convinced he's been on placebo 1106 01:07:24,260 --> 01:07:26,860 since the start of the trial. 1107 01:07:26,860 --> 01:07:30,540 Today's a day of mixed emotion cos there's excitement... 1108 01:07:32,180 --> 01:07:36,580 ..but there's fear that it won't work for me. 1109 01:07:42,460 --> 01:07:43,900 But there's no other show in town... 1110 01:07:45,700 --> 01:07:47,180 All right, Bryn. 1111 01:07:47,180 --> 01:07:49,220 ..so I'm kind of banking on it. 1112 01:07:55,740 --> 01:07:58,020 The pencil sharpener noise now. 1113 01:08:00,660 --> 01:08:02,180 My mum died when I was 14... 1114 01:08:03,660 --> 01:08:05,380 ..and I don't remember her as an adult. 1115 01:08:05,380 --> 01:08:07,500 I only remember her as a child. 1116 01:08:07,500 --> 01:08:10,380 I remember her as a mum, not as a person... 1117 01:08:10,380 --> 01:08:11,980 Go for 400 now. 400? 1118 01:08:11,980 --> 01:08:14,380 ..and I want my girls to know me as a grown-up... 1119 01:08:14,380 --> 01:08:16,180 All right, Bryn. We're off. 1120 01:08:17,180 --> 01:08:18,540 ..as a normal grown-up. 1121 01:08:22,940 --> 01:08:26,580 I can feel a warm tingling on my neck - that feels different. 1122 01:08:29,020 --> 01:08:31,580 Maybe I'm making it up, I don't know. I don't know! 1123 01:08:31,580 --> 01:08:32,860 She wouldn't tell me. 1124 01:08:37,060 --> 01:08:41,180 No-one will find out what they were on in the first nine months 1125 01:08:41,180 --> 01:08:43,220 until the end of the trial. 1126 01:08:44,820 --> 01:08:47,300 You don't want to artificially affect 1127 01:08:47,300 --> 01:08:49,620 how they feel in the second nine months 1128 01:08:49,620 --> 01:08:53,220 by letting them know what they were on in the first nine months. 1129 01:08:53,220 --> 01:08:56,860 They might have a heightened placebo response at that point 1130 01:08:56,860 --> 01:09:00,500 and generally it's better to keep the whole thing a secret 1131 01:09:00,500 --> 01:09:03,540 until you've collected all of your outcomes. 1132 01:09:06,420 --> 01:09:09,140 You know, I wanted to be a nun when I was younger. 1133 01:09:09,140 --> 01:09:12,060 Mind you, then I discovered that the shoes weren't very nice... 1134 01:09:13,460 --> 01:09:14,940 ..or the uniform. 1135 01:09:14,940 --> 01:09:18,860 As before, the volunteers come for monthly infusions. 1136 01:09:21,380 --> 01:09:23,260 And once every two months, 1137 01:09:23,260 --> 01:09:26,500 they're assessed off their conventional meds to see 1138 01:09:26,500 --> 01:09:30,140 if there's been any improvement in their baseline Parkinson's. 1139 01:09:32,820 --> 01:09:37,500 The role of the second nine months is to fulfil an obligation 1140 01:09:37,500 --> 01:09:41,660 set at the start of the trial by an independent ethics committee, 1141 01:09:41,660 --> 01:09:45,820 whose job it is to decide what's reasonable to ask volunteers to do. 1142 01:09:45,820 --> 01:09:51,460 It didn't seem ethical to put people through having brain surgery, 1143 01:09:51,460 --> 01:09:53,180 having the device inserted, 1144 01:09:53,180 --> 01:09:55,900 without ever having the prospect of the drug. 1145 01:09:58,100 --> 01:09:59,940 The second half of the trial 1146 01:09:59,940 --> 01:10:03,620 will also provide longer term safety and efficacy data. 1147 01:10:06,580 --> 01:10:10,220 OK, and look directly at the camera and smile, please. 1148 01:10:10,220 --> 01:10:11,740 They told me from day one, 1149 01:10:11,740 --> 01:10:13,020 "Don't read into things." 1150 01:10:13,020 --> 01:10:14,220 And frown. 1151 01:10:14,220 --> 01:10:16,060 "Don't try and analyse it." 1152 01:10:16,060 --> 01:10:18,860 And relax. Screw your eyes up really tight. 1153 01:10:20,100 --> 01:10:21,460 So I haven't. 1154 01:10:21,460 --> 01:10:23,380 And clench your teeth, please. 1155 01:10:24,620 --> 01:10:29,500 Volunteer Darren was diagnosed with Parkinson's 11 years ago. 1156 01:10:31,140 --> 01:10:33,540 The lack of expression in his face 1157 01:10:33,540 --> 01:10:36,180 is a typical feature of the condition. 1158 01:10:37,700 --> 01:10:43,300 I look like somebody who has got a disability, which I don't like. 1159 01:10:43,300 --> 01:10:44,260 Ready? Go. 1160 01:10:47,340 --> 01:10:50,180 It's like I'm trapped in my own body 1161 01:10:50,180 --> 01:10:53,820 and I'm desperate to get out. 1162 01:10:53,820 --> 01:10:55,660 That's what it feels like. 1163 01:10:57,860 --> 01:11:00,980 I just think I've got this for a reason. 1164 01:11:02,380 --> 01:11:04,780 I believe you've got to have trials. 1165 01:11:06,420 --> 01:11:07,980 OK. All right? 1166 01:11:07,980 --> 01:11:10,020 I want to make a difference for somebody. 1167 01:11:11,300 --> 01:11:15,300 If it's not me, I want to make a difference for somebody else. 1168 01:11:18,140 --> 01:11:21,740 Darren thinks he was on placebo in the first half of the trial. 1169 01:11:21,740 --> 01:11:24,620 This is his fourth infusion of GDNF 1170 01:11:24,620 --> 01:11:27,740 since the start of the second nine months. 1171 01:11:32,220 --> 01:11:33,900 Something's happening. 1172 01:11:33,900 --> 01:11:35,700 I don't know what. I'm not reading into it, 1173 01:11:35,700 --> 01:11:37,540 but something is definitely happening. 1174 01:11:37,540 --> 01:11:38,740 Up... CAT MEOWS 1175 01:11:38,740 --> 01:11:44,180 ..down, up, down, up, down, 1176 01:11:44,180 --> 01:11:46,060 and the more I'm doing it, 1177 01:11:46,060 --> 01:11:47,660 the more I'm smiling. 1178 01:11:47,660 --> 01:11:51,020 I'm thinking, "This ain't real. This ain't real." 1179 01:11:51,020 --> 01:11:53,580 And then I go downstairs and I start screaming to Jane, 1180 01:11:53,580 --> 01:11:56,020 "Come and see this. Come and see this." And she's going, 1181 01:11:56,020 --> 01:11:58,580 "What's the matter with you? What's the matter with you? 1182 01:11:58,580 --> 01:12:01,660 She got up and I said, "You've got to film this. This is unbelievable." 1183 01:12:01,660 --> 01:12:02,660 And now he's back! 1184 01:12:04,460 --> 01:12:06,220 Oh, dear. 1185 01:12:06,220 --> 01:12:08,740 I never expected none of this. 1186 01:12:08,740 --> 01:12:10,180 I never seen it coming. 1187 01:12:10,180 --> 01:12:12,340 That's pretty well amazing. 1188 01:12:12,340 --> 01:12:15,300 To be honest with you, it scared me a little bit. 1189 01:12:15,300 --> 01:12:18,540 INTERVIEWER: When was the last time you felt like that? 1190 01:12:18,540 --> 01:12:20,580 Before I had Parkinson's. 1191 01:12:21,660 --> 01:12:23,780 He's previously been quite guarded, 1192 01:12:23,780 --> 01:12:25,820 suddenly seems to have gone to the other end, 1193 01:12:25,820 --> 01:12:28,900 that he really feels this is a sort of dramatic response, 1194 01:12:28,900 --> 01:12:32,700 Lazarus type moment, and that he may be becoming free of Parkinson's. 1195 01:12:33,780 --> 01:12:37,340 Good morning. It's 6:30, would you believe? 1196 01:12:37,340 --> 01:12:40,900 He is now on 50% less medication 1197 01:12:40,900 --> 01:12:46,140 than he was on when he commenced on the double blind part of the trial. 1198 01:12:46,140 --> 01:12:51,460 And Darren has got me up to film him putting his socks on. 1199 01:12:51,460 --> 01:12:53,660 Can you believe this? 1200 01:12:53,660 --> 01:12:55,660 Unbelievable. 1201 01:12:55,660 --> 01:12:58,540 I just want to share these magic moments with her 1202 01:12:58,540 --> 01:13:00,340 and I think it is magic moments, 1203 01:13:00,340 --> 01:13:03,380 and just...just may it continue. 1204 01:13:09,300 --> 01:13:11,580 It seems to be starting. 1205 01:13:11,580 --> 01:13:14,220 A couple of things happened. 1206 01:13:14,220 --> 01:13:17,820 One, I just feel better, I've got a sense of wellbeing about me 1207 01:13:17,820 --> 01:13:19,260 and people say I'm looking better, 1208 01:13:19,260 --> 01:13:20,860 people say my voice sounds stronger. 1209 01:13:23,780 --> 01:13:26,220 One of the nurses independently said, 1210 01:13:26,220 --> 01:13:28,900 "Your facial expression has returned." 1211 01:13:28,900 --> 01:13:30,940 Can you give us a big smile? 1212 01:13:30,940 --> 01:13:32,260 And relax. 1213 01:13:32,260 --> 01:13:34,180 Can you frown? 1214 01:13:34,180 --> 01:13:36,780 Is this the light at the end of the tunnel? 1215 01:13:36,780 --> 01:13:40,100 Is this the beginning of the end? 1216 01:13:40,100 --> 01:13:42,020 And last of all, can you clench your teeth? 1217 01:13:45,860 --> 01:13:48,380 It's just awesome. 1218 01:13:48,380 --> 01:13:50,060 It is just awesome. 1219 01:13:56,700 --> 01:13:59,900 Look at my hands, you know, they're just... 1220 01:14:02,060 --> 01:14:04,180 I can type that, I've got dexterity 1221 01:14:04,180 --> 01:14:07,660 and I can throw darts right-handed to a fashion. 1222 01:14:07,660 --> 01:14:10,020 Not a fashion that's going to win me anything 1223 01:14:10,020 --> 01:14:12,300 but a fashion that keeps the wall safe. 1224 01:14:13,700 --> 01:14:15,700 That's not bad. 1225 01:14:15,700 --> 01:14:17,940 People send me up to the bar now to get drinks. 1226 01:14:17,940 --> 01:14:19,820 It's, er... 1227 01:14:20,820 --> 01:14:22,420 ..a real downside, actually, that. 1228 01:14:22,420 --> 01:14:24,100 Going to the bar to get drinks, 1229 01:14:24,100 --> 01:14:25,660 that's a real downside of being cured. 1230 01:14:27,180 --> 01:14:31,820 It's now a year since pharmaceutical giant Pfizer expressed interest 1231 01:14:31,820 --> 01:14:34,060 in GDNF and the Bristol delivery system. 1232 01:14:35,500 --> 01:14:38,700 The support of a major drug company is critical 1233 01:14:38,700 --> 01:14:41,980 if GDNF is to become a licensed treatment 1234 01:14:41,980 --> 01:14:43,980 available to everyone with Parkinson's. 1235 01:14:45,580 --> 01:14:47,660 That's because it costs millions 1236 01:14:47,660 --> 01:14:49,900 to do the further larger scale trials 1237 01:14:49,900 --> 01:14:52,660 required by the drug regulatory bodies. 1238 01:14:54,340 --> 01:14:57,580 Pfizer will also want to know which of Parkinson's many symptoms 1239 01:14:57,580 --> 01:14:58,820 the drug may help... 1240 01:15:00,940 --> 01:15:03,940 ..including the depression and cognitive decline 1241 01:15:03,940 --> 01:15:06,020 evident in patients like Ron Johnson. 1242 01:15:07,140 --> 01:15:10,780 Ron struggled in the first half of the trial. 1243 01:15:10,780 --> 01:15:12,300 Some days, I just... 1244 01:15:20,100 --> 01:15:22,260 I just don't understand what happens. 1245 01:15:25,580 --> 01:15:27,660 I do everything the same... 1246 01:15:29,500 --> 01:15:32,300 ..but Parky kicks the hell out of me. 1247 01:15:33,580 --> 01:15:36,740 Ron has now had seven infusions of GDNF. 1248 01:15:40,220 --> 01:15:44,580 When I first had Parkinson's, everything was uphill. 1249 01:15:44,580 --> 01:15:46,420 Now it's not. 1250 01:15:46,420 --> 01:15:49,140 You'll need to do it from the beginning, won't you? 1251 01:15:49,140 --> 01:15:50,620 Can you do it from your end? 1252 01:15:50,620 --> 01:15:52,620 It's made him more positive. 1253 01:15:53,820 --> 01:15:55,860 He's more there, more present. 1254 01:15:57,300 --> 01:16:01,420 What I mean is, you need to tie a knot in the string between them. 1255 01:16:01,420 --> 01:16:03,340 I think it will be all right once it's up. 1256 01:16:03,340 --> 01:16:05,220 It's a good life, basically. 1257 01:16:07,300 --> 01:16:10,300 And I think the GDNF has made a huge difference. 1258 01:16:13,340 --> 01:16:16,420 On a good day, I can do anything. 1259 01:16:16,420 --> 01:16:17,580 I really can. 1260 01:16:17,580 --> 01:16:18,620 WHIRRING 1261 01:16:22,500 --> 01:16:23,900 That was a good one. 1262 01:16:25,140 --> 01:16:27,340 Oh, God. Are you all right? Yeah. 1263 01:16:27,340 --> 01:16:29,420 It's just hit on your scar. 1264 01:16:29,420 --> 01:16:31,580 What scar? "What scar?" 1265 01:16:31,580 --> 01:16:33,660 Your scalp thing. 1266 01:16:33,660 --> 01:16:36,540 Where they took my brain out? Yeah. 1267 01:16:36,540 --> 01:16:38,940 INTERVIEWER: Would you have been tackling the kitchen 1268 01:16:38,940 --> 01:16:40,220 a couple of years ago? 1269 01:16:40,220 --> 01:16:41,700 No way. 1270 01:16:41,700 --> 01:16:43,020 Absolutely no way. 1271 01:16:45,060 --> 01:16:47,460 Make a mess of it now, but... 1272 01:16:51,140 --> 01:16:52,740 It's December 2015... 1273 01:16:53,940 --> 01:16:56,140 ..and the first volunteers to join the trial 1274 01:16:56,140 --> 01:16:58,980 are nearing the end of the second nine months. 1275 01:17:00,300 --> 01:17:04,140 There's now such optimism about GDNF's future 1276 01:17:04,140 --> 01:17:08,020 that Alan writes to invite them to continue their infusions 1277 01:17:08,020 --> 01:17:11,220 until everyone has completed their 18 months. 1278 01:17:12,580 --> 01:17:15,500 For some, it means several more infusions 1279 01:17:15,500 --> 01:17:17,460 than originally planned... 1280 01:17:17,460 --> 01:17:19,700 I'd like you to try and stand up out of the chair 1281 01:17:19,700 --> 01:17:21,020 without using your arms. 1282 01:17:21,020 --> 01:17:23,020 ..but there is no miracle yet for Tom. 1283 01:17:23,020 --> 01:17:24,020 Go. 1284 01:17:30,620 --> 01:17:33,380 Can you push off your arms at the side? 1285 01:17:34,820 --> 01:17:37,860 Push up from both arms of the chair, OK? 1286 01:17:37,860 --> 01:17:40,500 This morning I had my assessment... 1287 01:17:42,340 --> 01:17:43,700 ..and couldn't walk. 1288 01:17:45,140 --> 01:17:46,500 It led to... 1289 01:17:46,500 --> 01:17:47,620 No? 1290 01:17:48,820 --> 01:17:51,100 ..today I felt that 1291 01:17:51,100 --> 01:17:53,700 people are taking decisions away from me, 1292 01:17:53,700 --> 01:17:55,740 which were really mine to make. 1293 01:17:56,820 --> 01:17:59,580 The thing that I can't stand about this condition is 1294 01:17:59,580 --> 01:18:01,740 if it takes away control of my own life... 1295 01:18:02,900 --> 01:18:04,220 ..it's, er... 1296 01:18:05,820 --> 01:18:08,660 ..it's very tough to justify your existence. 1297 01:18:08,660 --> 01:18:12,100 Ready? Both, is it? Yep, at the same time. Ready, steady, go. 1298 01:18:17,260 --> 01:18:18,620 I can't take much more of this. 1299 01:18:20,300 --> 01:18:21,740 It sucks. 1300 01:18:24,180 --> 01:18:26,180 I don't like this disease. 1301 01:18:32,540 --> 01:18:35,980 Parkinson's is caused by the progressive death of cells 1302 01:18:35,980 --> 01:18:39,620 in the brain that produce a chemical called dopamine. 1303 01:18:41,260 --> 01:18:43,900 In the lab and in animal studies, 1304 01:18:43,900 --> 01:18:47,300 GDNF has been shown to regrow these cells... 1305 01:18:50,660 --> 01:18:53,860 OK, so it's just a little step just here, mind that one. 1306 01:18:53,860 --> 01:18:57,060 ..but Tom has now had Parkinson's for 20 years... 1307 01:18:59,540 --> 01:19:02,820 ..and it might simply be that it's too late. 1308 01:19:05,380 --> 01:19:08,540 But there's one other possibility. 1309 01:19:08,540 --> 01:19:11,300 Are you all right? I'm very well. How are you? 1310 01:19:11,300 --> 01:19:16,380 Tom is taken for an MRI scan and it shows that very little GDNF 1311 01:19:16,380 --> 01:19:18,420 is getting to the putamen - 1312 01:19:18,420 --> 01:19:21,620 the area of the brain they're trying to treat... 1313 01:19:23,300 --> 01:19:26,740 ..but it's not because of a problem in Tom's brain... 1314 01:19:27,860 --> 01:19:29,820 ..it's the delivery device. 1315 01:19:29,820 --> 01:19:34,460 Nobody's ever tried to deliver drugs in this way repeatedly 1316 01:19:34,460 --> 01:19:36,100 in somebody with a disease 1317 01:19:36,100 --> 01:19:39,340 where they're moving their brain around all the time. 1318 01:19:39,340 --> 01:19:42,140 So we're learning as we're going along. 1319 01:19:43,300 --> 01:19:45,660 As one of the first to have surgery, 1320 01:19:45,660 --> 01:19:48,300 Tom has an early version of the device 1321 01:19:48,300 --> 01:19:50,300 that delivers GDNF to the brain. 1322 01:19:51,980 --> 01:19:54,220 Steve now has a new version - 1323 01:19:54,220 --> 01:19:56,860 one that will ensure that more drug reaches 1324 01:19:56,860 --> 01:19:58,900 and stays in the right place. 1325 01:20:00,820 --> 01:20:02,980 Tom is offered the new device. 1326 01:20:05,540 --> 01:20:09,020 To go through all that again is a very big undertaking for him, 1327 01:20:09,020 --> 01:20:13,340 but I think this is the only choice he has - 1328 01:20:13,340 --> 01:20:18,540 either he goes for this opportunity or he comes out of the trial. 1329 01:20:21,820 --> 01:20:24,460 I'm crazy, going back for surgery again. 1330 01:20:25,780 --> 01:20:30,060 Why have I got such belief in this man, Steven Gill? 1331 01:20:39,460 --> 01:20:41,940 I've just got a bad feeling that... 1332 01:20:44,500 --> 01:20:46,780 ..sort of, what'll happen if I have the surgery again? 1333 01:20:49,380 --> 01:20:50,980 Something bad is going to happen... 1334 01:20:55,580 --> 01:20:57,500 ..but I can't tell Lindsay that. 1335 01:21:00,700 --> 01:21:03,420 Just to go through why we're doing this. 1336 01:21:03,420 --> 01:21:06,460 The catheters that you've got at the moment a relatively vertical. 1337 01:21:06,460 --> 01:21:08,300 I think, because of your dyskinesia, 1338 01:21:08,300 --> 01:21:10,540 what happens is, the brain is moving around like this, 1339 01:21:10,540 --> 01:21:13,060 the catheters are also moving 1340 01:21:13,060 --> 01:21:15,660 and that's causing reflux. 1341 01:21:15,660 --> 01:21:19,900 What we have done in the interim is develop a new catheter 1342 01:21:19,900 --> 01:21:23,140 which performs completely differently. 1343 01:21:23,140 --> 01:21:25,940 And you've tried it in people who have dyskinesia? Yes. Right. 1344 01:21:25,940 --> 01:21:27,780 Yeah. And we put it in... 1345 01:21:27,780 --> 01:21:30,260 As bad as mine is? 1346 01:21:30,260 --> 01:21:32,540 Now that would be challenging. HE LAUGHS 1347 01:21:32,540 --> 01:21:34,060 Charming! 1348 01:21:34,060 --> 01:21:37,580 And in Tom's scan, is there anything different from the first one? 1349 01:21:37,580 --> 01:21:40,020 Did you not...? No, I'm just impressed by the amount 1350 01:21:40,020 --> 01:21:41,980 of grey matter that you have. Fantastic. 1351 01:21:41,980 --> 01:21:43,820 TOM CHUCKLES 1352 01:21:45,460 --> 01:21:46,900 See you later. 1353 01:21:53,620 --> 01:21:57,460 I think this will be absolutely the right thing to do. 1354 01:21:59,860 --> 01:22:02,420 One way or another, you absolutely have to get him right, 1355 01:22:02,420 --> 01:22:03,780 as best as we can. 1356 01:22:10,500 --> 01:22:13,300 So now, if we just bring him around this way and we can put him 1357 01:22:13,300 --> 01:22:15,100 on the table that way. 1358 01:22:15,100 --> 01:22:18,820 So, on this? Yeah. Just one point. 1359 01:22:18,820 --> 01:22:22,860 The new kit will be put in via the back of Tom's head, 1360 01:22:22,860 --> 01:22:25,260 yet another refinement. 1361 01:22:25,260 --> 01:22:29,940 First, the old kit has to come out through the top of Tom's head. 1362 01:22:31,460 --> 01:22:32,580 Later. 1363 01:22:34,180 --> 01:22:35,860 On ten, is it? 1364 01:22:35,860 --> 01:22:37,180 Yes, cutting around. 1365 01:22:41,260 --> 01:22:44,260 The ones we've just looked at are very good. 1366 01:22:44,260 --> 01:22:47,860 The procedure requires sub-millimetre accuracy. 1367 01:22:47,860 --> 01:22:50,460 Have you got a swab I could use, please? 1368 01:22:50,460 --> 01:22:52,260 Just got one more to put in. 1369 01:22:53,620 --> 01:22:56,180 The target is in a deep part of the brain 1370 01:22:56,180 --> 01:22:59,380 where hitting a major blood vessel could be fatal. 1371 01:23:03,900 --> 01:23:06,220 Yep, and now go that way. 1372 01:23:06,220 --> 01:23:10,020 After six hours, a portable CT scanner is brought in to check 1373 01:23:10,020 --> 01:23:13,180 that the four new catheters are in exactly the right place. 1374 01:23:13,180 --> 01:23:14,540 Why are we so deep? 1375 01:23:16,500 --> 01:23:17,900 Shoot. 1376 01:23:17,900 --> 01:23:21,540 The scan shows clearly that one of the catheters 1377 01:23:21,540 --> 01:23:23,180 has veered off target. 1378 01:23:23,180 --> 01:23:25,980 Oh, there it is. Yeah, you can see it there. Yeah, yeah. 1379 01:23:27,420 --> 01:23:28,860 Flicked about there. Yeah. 1380 01:23:28,860 --> 01:23:30,980 Just flicked up. That's... 1381 01:23:30,980 --> 01:23:32,740 That's... I think... 1382 01:23:32,740 --> 01:23:35,140 I think I felt something as I went in. 1383 01:23:35,140 --> 01:23:38,020 It felt like a vessel and there are some vessels there. 1384 01:23:38,020 --> 01:23:39,580 Let's have a look at this here. 1385 01:23:39,580 --> 01:23:41,300 Some vessels there, look. Mmm. 1386 01:23:43,500 --> 01:23:45,420 And that's why it's deflected off. 1387 01:23:46,580 --> 01:23:47,940 I hit the side of a vessel. 1388 01:23:47,940 --> 01:23:50,900 It's so tight, it's like a slalom. 1389 01:23:50,900 --> 01:23:54,460 So one is working in very, very tight area. 1390 01:23:54,460 --> 01:23:56,060 Look at that. 1391 01:23:57,100 --> 01:24:00,420 It's a major vessel in the neck that obviously could cause major 1392 01:24:00,420 --> 01:24:02,500 disability or could be fatal. 1393 01:24:02,500 --> 01:24:03,940 I mean, worst case scenario. 1394 01:24:06,460 --> 01:24:11,100 These are the old catheters and they had a very short trajectory 1395 01:24:11,100 --> 01:24:12,780 which went just down to here. 1396 01:24:12,780 --> 01:24:16,860 So they were about a third of the length of these very long catheters 1397 01:24:16,860 --> 01:24:19,620 which will now fill this whole structure up. 1398 01:24:21,540 --> 01:24:24,700 Tom has been in surgery for nine hours. 1399 01:24:28,020 --> 01:24:29,380 Can you do that? 1400 01:24:29,380 --> 01:24:31,780 Yeah. Yeah, perfect. 1401 01:24:31,780 --> 01:24:33,820 Can you wiggle your toes for me? 1402 01:24:35,780 --> 01:24:37,340 Have you got any pain anywhere? 1403 01:24:37,340 --> 01:24:40,180 We kind of blased into this one. 1404 01:24:40,180 --> 01:24:44,460 Having been through it already, we thought it was going to be OK 1405 01:24:44,460 --> 01:24:45,980 and, er... 1406 01:24:47,100 --> 01:24:51,780 ..unfortunately Tom had quite severe post-operative complications. 1407 01:24:53,140 --> 01:24:55,300 To put the catheter in from the back of the head, 1408 01:24:55,300 --> 01:24:57,900 you have to have the patient operated on face down. 1409 01:24:57,900 --> 01:25:00,500 If they're there for many hours, particularly if you have, 1410 01:25:00,500 --> 01:25:02,620 as in Tom's case, you had to take out the old system, 1411 01:25:02,620 --> 01:25:04,860 so that's a big operation its own right. 1412 01:25:04,860 --> 01:25:07,260 And then put it in a completely new system, 1413 01:25:07,260 --> 01:25:09,260 it's many hours with him on his face, 1414 01:25:09,260 --> 01:25:13,300 and during that time, because he was quite flexed, 1415 01:25:13,300 --> 01:25:18,780 the intubation tube caused pressure effects inside his throat. 1416 01:25:18,780 --> 01:25:21,820 And so, when he woke up, he had a swollen tongue. 1417 01:25:21,820 --> 01:25:24,220 He had difficulty breathing and he got very distressed. 1418 01:25:25,700 --> 01:25:28,780 He's having a really tough time at the moment and... 1419 01:25:30,180 --> 01:25:32,660 ..it's incredibly hard on both of us. 1420 01:25:40,420 --> 01:25:43,380 I will. You will. 1421 01:26:05,900 --> 01:26:09,980 This last little session that I've been through 1422 01:26:09,980 --> 01:26:12,180 has been the most appalling. 1423 01:26:14,380 --> 01:26:17,460 I thought I was going to die. 1424 01:26:17,460 --> 01:26:21,340 But I just had faith in this treatment, in the team. 1425 01:26:24,420 --> 01:26:28,020 Even if I'm not cured, I will strike a happy medium somewhere. 1426 01:26:30,460 --> 01:26:32,860 I've got nothing to fear any more. 1427 01:26:32,860 --> 01:26:35,540 I can deal with this silly illness, 1428 01:26:35,540 --> 01:26:37,500 whatever it throws at me, 1429 01:26:37,500 --> 01:26:41,220 as long as... The only thing I ask is I need to be able to communicate. 1430 01:26:44,700 --> 01:26:46,700 We always get stronger in times like this. 1431 01:26:46,700 --> 01:26:48,860 I think it brings us together. 1432 01:26:51,820 --> 01:26:53,900 INTERVIEWER: Does there come a point where you say, 1433 01:26:53,900 --> 01:26:55,420 "Enough is enough"? 1434 01:26:55,420 --> 01:26:58,380 Maybe, but not yet. Not yet. 1435 01:26:58,380 --> 01:27:00,100 Absolutely not. 1436 01:27:06,540 --> 01:27:08,260 Does that feel all right, Tom? 1437 01:27:08,260 --> 01:27:10,180 Yeah, that's fine. Yeah? 1438 01:27:13,620 --> 01:27:18,620 This port is 100% better than the original. 1439 01:27:18,620 --> 01:27:20,620 I cannot actually believe... 1440 01:27:21,660 --> 01:27:22,740 ..how... 1441 01:27:24,540 --> 01:27:28,340 ..they've managed to perfect this in such a short time, 1442 01:27:28,340 --> 01:27:31,980 but the first time Tom had this done, it took... 1443 01:27:31,980 --> 01:27:34,860 ..erm, six weeks to heal. 1444 01:27:34,860 --> 01:27:36,260 How does it feel? 1445 01:27:36,260 --> 01:27:38,740 Can you feel anything on it, Tom? No, can't feel anything. 1446 01:27:38,740 --> 01:27:41,740 The only problem is, it's on my starboard side. Right. 1447 01:27:49,740 --> 01:27:53,100 Three weeks later, Tom resumes his infusions. 1448 01:28:03,700 --> 01:28:06,380 There are now just a few weeks of the trial to go. 1449 01:28:07,500 --> 01:28:13,220 The impression I'm getting is that more people are improving. 1450 01:28:17,660 --> 01:28:19,380 And that's perhaps not surprising, 1451 01:28:19,380 --> 01:28:22,620 given that everybody's now on the active drug. 1452 01:28:22,620 --> 01:28:25,420 Don't eat too much. We're having dinner in an hour and a half. 1453 01:28:25,420 --> 01:28:27,540 Who's your favourite daughter? 1454 01:28:27,540 --> 01:28:29,060 Favourite daughter? 1455 01:28:29,060 --> 01:28:31,140 You're in the top two. 1456 01:28:32,380 --> 01:28:35,420 And people who appear to be improving 1457 01:28:35,420 --> 01:28:38,220 during the first nine months are potentially improving 1458 01:28:38,220 --> 01:28:41,700 yet further still in the second nine months. 1459 01:28:42,900 --> 01:28:45,180 In Cornwall, volunteer Kay Cotton 1460 01:28:45,180 --> 01:28:49,420 is convinced she's been on the real thing since the start. 1461 01:28:49,420 --> 01:28:51,740 My Parkinson's was in my left-hand side. 1462 01:28:51,740 --> 01:28:55,700 I said "was" in my life-hand side cos that's what it feels like now. 1463 01:28:55,700 --> 01:28:57,540 Both sides feel as loose as each other 1464 01:28:57,540 --> 01:29:00,380 and I couldn't do this before, I hope I can do it now! 1465 01:29:07,100 --> 01:29:08,860 Ready, steady, go. 1466 01:29:10,340 --> 01:29:13,660 It's volunteer Vicky Dillon's final assessment of the trial. 1467 01:29:17,820 --> 01:29:19,260 And it's a revelation. 1468 01:29:20,900 --> 01:29:22,980 It was like... 1469 01:29:22,980 --> 01:29:28,220 I was almost better off my meds the longer I went on. 1470 01:29:31,460 --> 01:29:34,140 I can't explain it and we can't get our heads round it, 1471 01:29:34,140 --> 01:29:36,340 but it was like a bloody miracle! 1472 01:29:41,380 --> 01:29:43,540 It's not just yesterday. 1473 01:29:43,540 --> 01:29:46,820 The amount of people who come to me and tell me that I look better... 1474 01:29:47,940 --> 01:29:50,740 I know I'm better! There's no doubt in my mind. 1475 01:29:59,300 --> 01:30:03,540 It's now three years since Tom Isaacs started on the trial. 1476 01:30:03,540 --> 01:30:07,820 Despite many setbacks, his faith in the Bristol team 1477 01:30:07,820 --> 01:30:10,380 and in GDNF has been unshakeable. 1478 01:30:16,860 --> 01:30:19,260 22nd of July, 1479 01:30:19,260 --> 01:30:21,420 2015. 1480 01:30:23,220 --> 01:30:26,500 Here we are again in Bristol. 1481 01:30:26,500 --> 01:30:30,180 And what is happening tomorrow is another off assessment. 1482 01:30:30,180 --> 01:30:34,380 My second off assessment since my second bout of surgery. 1483 01:30:35,820 --> 01:30:39,500 And I'm hoping... 1484 01:30:40,660 --> 01:30:45,660 ..there might be a bit of something to show for my efforts. 1485 01:30:49,060 --> 01:30:51,460 The date you were diagnosed on your first symptom. 1486 01:30:51,460 --> 01:30:53,740 I was diagnosed in 1996, 1487 01:30:53,740 --> 01:30:58,580 and my first symptom was a tremor in my right hand. 1488 01:30:58,580 --> 01:30:59,900 I've got this... 1489 01:31:01,780 --> 01:31:03,260 Just a little part of me 1490 01:31:03,260 --> 01:31:06,100 is hoping that something wonderful is going to happen. 1491 01:31:07,540 --> 01:31:08,740 Ready, steady, go. 1492 01:31:11,620 --> 01:31:15,060 Compared to when he was assessed off his regular meds four months ago... 1493 01:31:16,660 --> 01:31:19,140 ..Tom is 50% better. 1494 01:31:21,580 --> 01:31:23,380 Last time I did the off assessment, 1495 01:31:23,380 --> 01:31:25,300 I couldn't even start the walk of death. 1496 01:31:27,940 --> 01:31:30,260 No. 1497 01:31:30,260 --> 01:31:32,100 Tomorrow, I've got a chance 1498 01:31:32,100 --> 01:31:33,940 I'll be able to make it 1499 01:31:33,940 --> 01:31:38,020 and if I do make it, it's going to be an eureka moment. 1500 01:31:38,020 --> 01:31:39,020 Go. 1501 01:31:58,500 --> 01:32:00,340 Come on! Come on! 1502 01:32:01,460 --> 01:32:03,300 Do this thing! 1503 01:32:09,340 --> 01:32:11,100 Yes! 1504 01:32:12,820 --> 01:32:14,340 Well done! 1505 01:32:17,620 --> 01:32:19,820 Love Alan, 1506 01:32:19,820 --> 01:32:21,500 love Steve, 1507 01:32:21,500 --> 01:32:23,700 love Lucy, love them all. 1508 01:32:27,300 --> 01:32:29,700 And when they make me better, 1509 01:32:29,700 --> 01:32:31,380 when they make all of us better... 1510 01:32:34,460 --> 01:32:37,420 ..we'll have a big party 1511 01:32:37,420 --> 01:32:40,900 and I'm going to get very, very drunk! 1512 01:32:48,260 --> 01:32:49,860 July 2016. 1513 01:32:53,220 --> 01:32:58,140 It's now 23 years since a researcher in America put GDNF 1514 01:32:58,140 --> 01:33:00,700 onto a dying dopamine brain cell... 1515 01:33:04,020 --> 01:33:05,940 ..and saw it come back to life. 1516 01:33:08,820 --> 01:33:12,860 It's 15 years since Steve Gill first tried the drug in humans. 1517 01:33:14,940 --> 01:33:18,340 And 12 years since GDNF was dropped 1518 01:33:18,340 --> 01:33:21,060 after a failed trial in 2004. 1519 01:33:23,220 --> 01:33:26,100 The drug's future and the future for the millions of people 1520 01:33:26,100 --> 01:33:29,700 worldwide with Parkinson's hangs in the balance. 1521 01:33:29,700 --> 01:33:31,580 It's results day. 1522 01:33:36,420 --> 01:33:37,820 Afternoon. Hello. 1523 01:33:37,820 --> 01:33:40,060 Big day. Very big day. 1524 01:33:40,060 --> 01:33:41,260 Yes. 1525 01:33:42,620 --> 01:33:45,620 And I'm just really relieved we've got to the point of having 1526 01:33:45,620 --> 01:33:47,820 the answer for the first nine months, 1527 01:33:47,820 --> 01:33:50,460 so that's terrific that we've got to the point, 1528 01:33:50,460 --> 01:33:54,620 knowing what the result is - the data will be the data. 1529 01:33:54,620 --> 01:33:57,980 But I'm very pleased to be here, so... 1530 01:34:00,420 --> 01:34:02,940 The CEO of the small bio-tech company that has 1531 01:34:02,940 --> 01:34:06,500 the patent on GDNF has flown in from Canada. 1532 01:34:10,100 --> 01:34:12,740 Erich Mohr has put millions of dollars of his own 1533 01:34:12,740 --> 01:34:14,580 money into the venture. 1534 01:34:14,580 --> 01:34:15,700 I feel good. 1535 01:34:15,700 --> 01:34:18,060 I mean, you know, obviously, I'm an optimist, 1536 01:34:18,060 --> 01:34:21,740 so hopefully, on behalf of the ten million patients, which is the 1537 01:34:21,740 --> 01:34:26,140 most important part, we had success today, but science will be science. 1538 01:34:31,460 --> 01:34:35,140 And you don't have any idea what the results are? I do not. 1539 01:34:35,140 --> 01:34:38,380 And you're still able to be that optimistic? I am. 1540 01:34:38,380 --> 01:34:40,380 Famous last words! 1541 01:34:40,380 --> 01:34:42,580 INDISTINCT 1542 01:34:43,620 --> 01:34:46,380 Mr Mohr. 1543 01:34:46,380 --> 01:34:49,140 Big day today. Big day, yup. 1544 01:34:57,580 --> 01:35:00,700 The trial steering committee includes scientists, 1545 01:35:00,700 --> 01:35:03,780 the medical team, engineers, 1546 01:35:03,780 --> 01:35:06,860 and representatives from the charities that funded the trial. 1547 01:35:09,380 --> 01:35:11,100 To remind you, 1548 01:35:11,100 --> 01:35:14,940 we needed to see a 20% difference at the end of the study 1549 01:35:14,940 --> 01:35:19,500 between the treated group with GDNF versus the placebo group, 1550 01:35:19,500 --> 01:35:21,980 so there needed to be a 20% difference and that's what 1551 01:35:21,980 --> 01:35:26,900 we needed to reach, statistical significance, at a group level. 1552 01:35:31,500 --> 01:35:33,260 And the answer is... 1553 01:35:36,500 --> 01:35:38,860 ..that sadly we did not meet the primary endpoint. 1554 01:36:04,820 --> 01:36:09,540 Everybody in the room was in a state of shock. Couldn't speak. 1555 01:36:09,540 --> 01:36:11,620 That's how bad it was. 1556 01:36:11,620 --> 01:36:14,860 I've never been in any environment where that's happened like that 1557 01:36:14,860 --> 01:36:17,220 because there was such expectation. 1558 01:36:18,740 --> 01:36:21,180 It was the end of hope, I think. 1559 01:36:21,180 --> 01:36:22,940 That's how it felt. 1560 01:36:24,220 --> 01:36:27,900 Not only for me, but for the ten million or so individuals who 1561 01:36:27,900 --> 01:36:32,740 suffer from Parkinson's disease, this is a huge disappointment. 1562 01:36:32,740 --> 01:36:36,420 But it is perhaps an important reminder why 1563 01:36:36,420 --> 01:36:40,700 we do clinical trials the way we do them, so that they're not 1564 01:36:40,700 --> 01:36:43,900 done on hunches or guesses, but on objective measures. 1565 01:36:47,180 --> 01:36:50,980 The group on GDNF did do better than those in the placebo group... 1566 01:36:52,620 --> 01:36:54,500 ..but it needed to be by 20% 1567 01:36:54,500 --> 01:36:57,940 to be considered statistically significant. 1568 01:36:57,940 --> 01:36:59,940 And it was only by 6%. 1569 01:37:01,380 --> 01:37:02,660 In other words, 1570 01:37:02,660 --> 01:37:05,580 the improvement could have been down to chance alone. 1571 01:37:08,780 --> 01:37:12,980 We hadn't just slightly missed, we'd missed by a country mile, 1572 01:37:12,980 --> 01:37:14,460 in statistical terms. 1573 01:37:16,780 --> 01:37:19,660 The negative result almost certainly means 1574 01:37:19,660 --> 01:37:22,140 it's the end of the road for GDNF. 1575 01:37:25,980 --> 01:37:29,780 It falls to Alan to tell the volunteers, via a conference call. 1576 01:37:33,340 --> 01:37:35,820 Now, before I go on, what I wanted to say first 1577 01:37:35,820 --> 01:37:37,820 was a massive thank you, 1578 01:37:37,820 --> 01:37:42,540 on behalf of all the trial team here, to you the participants. 1579 01:37:42,540 --> 01:37:45,940 We could not have done this without you. 1580 01:37:45,940 --> 01:37:48,340 However, unfortunately, 1581 01:37:48,340 --> 01:37:53,180 there was not a statistically significant improvement 1582 01:37:53,180 --> 01:37:55,500 in people receiving GDNF 1583 01:37:55,500 --> 01:37:58,660 compared to those receiving placebo at the nine month point 1584 01:37:58,660 --> 01:38:00,900 in their motor scores, 1585 01:38:00,900 --> 01:38:03,540 when assessed off regular Parkinson's medication. 1586 01:38:05,540 --> 01:38:07,980 I know that comes as a disappointment. 1587 01:38:07,980 --> 01:38:10,140 I'm going to say more now. 1588 01:38:10,140 --> 01:38:13,900 The group who received GDNF did not significantly do better than 1589 01:38:13,900 --> 01:38:16,340 the group who received placebo on this measure, 1590 01:38:16,340 --> 01:38:20,860 by significance we mean a statistically significant effect. 1591 01:38:20,860 --> 01:38:24,340 We know that individuals, 1592 01:38:24,340 --> 01:38:29,500 they have felt they did better to a greater or lesser extent. 1593 01:38:29,500 --> 01:38:32,140 I'd love to be able to talk to each of you face to face right now. 1594 01:38:32,140 --> 01:38:34,220 You are all incredibly dear to me. 1595 01:38:34,220 --> 01:38:38,020 I'm enormously grateful for what you've taken part in. 1596 01:38:38,020 --> 01:38:41,900 I still think it's been worth doing. 1597 01:38:41,900 --> 01:38:44,380 And I don't, myself, 1598 01:38:44,380 --> 01:38:47,660 regret a day that I've spent working on this trial. 1599 01:38:47,660 --> 01:38:51,260 And I wish everybody luck, including all the trial team... 1600 01:38:51,260 --> 01:38:53,100 Bollocks. 1601 01:38:57,380 --> 01:38:59,380 That is... 1602 01:39:01,020 --> 01:39:03,780 ..slightly disappointing. 1603 01:39:03,780 --> 01:39:05,980 It's had a huge impact on all of us. 1604 01:39:09,340 --> 01:39:11,180 I just think... 1605 01:39:12,380 --> 01:39:14,620 ..has it even been worth it? 1606 01:39:17,820 --> 01:39:20,340 Better start applying for my blue badge. 1607 01:39:21,940 --> 01:39:24,460 And, um... 1608 01:39:29,420 --> 01:39:31,300 ..looking out for a fucking bungalow. 1609 01:39:47,860 --> 01:39:49,980 We know that patients said they felt better, 1610 01:39:49,980 --> 01:39:53,460 but we weren't able to prove it against placebo and what that means 1611 01:39:53,460 --> 01:39:57,660 is we haven't shown benefit, we haven't proved it, it's not enough. 1612 01:40:02,020 --> 01:40:07,420 But then, a more in-depth look at the data reveals some anomalies. 1613 01:40:09,460 --> 01:40:11,380 The trial failed because, overall, 1614 01:40:11,380 --> 01:40:15,140 the volunteers on GDNF didn't perform significantly better 1615 01:40:15,140 --> 01:40:18,420 than those on placebo when off their regular Parkinson's meds. 1616 01:40:20,260 --> 01:40:23,300 This is what's called the primary outcome measure. 1617 01:40:25,660 --> 01:40:28,980 Every trial has one and it's the measure by which the overall 1618 01:40:28,980 --> 01:40:30,540 success of trials are judged. 1619 01:40:33,300 --> 01:40:37,500 But the GDNF trial recorded much more than just movement scores. 1620 01:40:39,900 --> 01:40:42,380 I can do that. I'm used to shuffling! 1621 01:40:42,380 --> 01:40:44,980 In particular, at the start of the trial 1622 01:40:44,980 --> 01:40:49,300 and again after nine months, all the volunteers had a scan which 1623 01:40:49,300 --> 01:40:52,540 measured the amount of dopamine in their brains. 1624 01:40:52,540 --> 01:40:57,100 We've started scanning, OK? Just keep really still, all right? 1625 01:40:57,100 --> 01:41:01,100 What we see in patients prior to the trial 1626 01:41:01,100 --> 01:41:03,380 is that there's insufficient dopamine 1627 01:41:03,380 --> 01:41:05,700 in these deeper structures in the brain 1628 01:41:05,700 --> 01:41:09,260 and that's what we'd see generally in people with Parkinson's disease. 1629 01:41:11,020 --> 01:41:14,300 PET scans use a radioactive tracer to measure 1630 01:41:14,300 --> 01:41:17,140 the amount of dopamine nerve endings in the brain. 1631 01:41:18,820 --> 01:41:24,820 After nine months, those who'd been on placebo showed no change. 1632 01:41:27,300 --> 01:41:30,540 And then, they looked at the PET scans of those who'd been on GDNF. 1633 01:41:32,060 --> 01:41:34,860 Having delivered GDNF to these patients, 1634 01:41:34,860 --> 01:41:38,220 we've seen that signal throughout the whole of that structure 1635 01:41:38,220 --> 01:41:40,180 increase, by 100%. 1636 01:41:43,660 --> 01:41:45,180 So, that's a large effect. 1637 01:41:46,540 --> 01:41:51,460 The nerve endings in the putamen part of the brain have regenerated. 1638 01:41:53,220 --> 01:41:56,060 Whilst that doesn't mean those nerves were working well, 1639 01:41:56,060 --> 01:42:00,140 it does mean there was some biological response. 1640 01:42:00,140 --> 01:42:04,220 So, now, we've got to work out why, despite that good delivery, 1641 01:42:04,220 --> 01:42:07,540 achieving that biological effect, we didn't bring through a large 1642 01:42:07,540 --> 01:42:10,580 enough clinical benefit to see statistical significance. 1643 01:42:13,180 --> 01:42:17,620 The team then looks in detail at who was and wasn't on placebo. 1644 01:42:19,100 --> 01:42:24,020 Today, after almost three years of waiting, 1645 01:42:24,020 --> 01:42:27,540 I've finally come to see Alan to find out 1646 01:42:27,540 --> 01:42:33,580 if I was on the placebo or GDNF and to get my results. 1647 01:42:36,060 --> 01:42:38,940 Nick did not think he was any better at the end of the first 1648 01:42:38,940 --> 01:42:41,180 half of the trial 1649 01:42:41,180 --> 01:42:43,260 and is pretty sure he was on placebo. 1650 01:42:47,460 --> 01:42:51,980 So, for the first nine months, in fact, you were on placebo. OK. 1651 01:42:54,580 --> 01:42:56,540 Fine. OK? 1652 01:42:57,620 --> 01:43:00,300 In fact, there weren't many surprises. 1653 01:43:01,980 --> 01:43:06,260 Bryn, who had not felt better at the end of the first nine months... 1654 01:43:06,260 --> 01:43:09,660 I'm expecting my assessment to show my continual decline through 1655 01:43:09,660 --> 01:43:12,700 the first half the trial. ..was also on placebo. 1656 01:43:15,100 --> 01:43:17,220 I honestly think I'm on the placebo. 1657 01:43:17,220 --> 01:43:19,220 I haven't felt no different whatsoever. 1658 01:43:21,620 --> 01:43:23,260 And so was Jeff. 1659 01:43:25,300 --> 01:43:29,340 Vicki, who improved from the start, was on GDNF. 1660 01:43:31,620 --> 01:43:35,060 And so... See? No tremor. ..was Kay. 1661 01:43:35,060 --> 01:43:38,500 Well, very little tremor. This is my hand that usually tremors a lot. 1662 01:43:40,140 --> 01:43:43,580 But Ron, who was fed up in the first nine months... 1663 01:43:43,580 --> 01:43:47,060 If this is as good as it gets, I'll be pissed off. 1664 01:43:47,060 --> 01:43:49,220 ..was on the real drug from the start. 1665 01:43:56,100 --> 01:44:00,020 Tom got significantly worse in the first nine months, 1666 01:44:00,020 --> 01:44:02,580 despite being on GDNF all along. 1667 01:44:05,300 --> 01:44:08,020 Come on! But by the end of the trial... Do this thing! 1668 01:44:08,020 --> 01:44:10,380 ..Tom's scores were back to what they'd 1669 01:44:10,380 --> 01:44:14,260 been at the start of the trial, four years previously. 1670 01:44:14,260 --> 01:44:17,100 Potentially significant... Yes! 1671 01:44:17,100 --> 01:44:19,540 ..because Parkinson's gets worse over time. 1672 01:44:21,060 --> 01:44:25,020 The higher the score, the more severe the problem. OK. 1673 01:44:25,020 --> 01:44:28,420 The natural course of the condition means that Nick's movement 1674 01:44:28,420 --> 01:44:33,460 scores should be about 3% worse than at the start of the trial. 1675 01:44:33,460 --> 01:44:36,820 So, you've improved by 66%... Wow! 1676 01:44:36,820 --> 01:44:42,420 ..in your off scores by the end... Wow! 1677 01:44:44,100 --> 01:44:47,380 That's quite... That's quite amazing! 1678 01:44:47,380 --> 01:44:51,180 You know that natural progression will be about two points per year. 1679 01:44:51,180 --> 01:44:53,620 Four of the 41 patients who finished 1680 01:44:53,620 --> 01:44:56,900 the trial did not get better overall. 1681 01:44:58,540 --> 01:45:03,180 But Ron's motor scores improved by 11% by the end of the trial. 1682 01:45:08,380 --> 01:45:09,900 Bryn's by 20%. 1683 01:45:12,100 --> 01:45:13,620 And bring them into your chest. 1684 01:45:22,700 --> 01:45:26,340 And Kay was 23% better. Further apart. 1685 01:45:29,580 --> 01:45:31,620 And forward. 1686 01:45:35,500 --> 01:45:39,180 Overall, Jeff's motor scores stayed much the same, 1687 01:45:39,180 --> 01:45:43,820 but his walking was three times better by the end of the trial. 1688 01:45:47,300 --> 01:45:50,540 Darren improved across the board, by 50%. 1689 01:45:53,940 --> 01:45:55,860 And by the end of the trial, 1690 01:45:55,860 --> 01:45:59,220 Vicki had improved by more than 60%. 1691 01:46:03,140 --> 01:46:07,420 By the time we get to the end of the second nine months, 1692 01:46:07,420 --> 01:46:11,660 the average improvement was between, overall, 1693 01:46:11,660 --> 01:46:13,540 a moderate to a large clinical effect. 1694 01:46:15,220 --> 01:46:18,700 Pfizer's interest was contingent on the first nine months 1695 01:46:18,700 --> 01:46:19,900 being a success. 1696 01:46:22,260 --> 01:46:27,140 But the secondary findings are enough to keep them at the table. 1697 01:46:27,140 --> 01:46:30,780 Hopes rise that the volunteers could resume infusions 1698 01:46:30,780 --> 01:46:33,060 as part of a longer-term study. 1699 01:46:34,900 --> 01:46:39,620 And so everything seems to be moving gradually, gradually towards, 1700 01:46:39,620 --> 01:46:41,300 you know, a phase three study. 1701 01:46:43,700 --> 01:46:46,340 In March 2017, there's an event in Bristol 1702 01:46:46,340 --> 01:46:49,260 to mark the end of the trial. 1703 01:46:49,260 --> 01:46:52,940 It brings all the volunteers together for the first time. 1704 01:46:52,940 --> 01:46:54,740 Some of the Parkinson's assessments 1705 01:46:54,740 --> 01:46:56,860 of the trial were certainly ridiculous. 1706 01:46:56,860 --> 01:46:58,980 One of the questions I was asked was, 1707 01:46:58,980 --> 01:47:02,220 "Over the past few weeks, have you been more or less indecisive?" 1708 01:47:03,540 --> 01:47:05,700 To which there is only one answer - "I'm not sure." 1709 01:47:05,700 --> 01:47:07,340 LAUGHTER 1710 01:47:07,340 --> 01:47:10,380 I am here today to tell you, first of all, thank you from the bottom 1711 01:47:10,380 --> 01:47:14,220 of our hearts that you have embarked on this mission. 1712 01:47:14,220 --> 01:47:17,860 This quest, by the way, many people have likened to 1713 01:47:17,860 --> 01:47:19,340 a manned mission to Mars. 1714 01:47:19,340 --> 01:47:21,340 Well, folks, you are the travellers. 1715 01:47:21,340 --> 01:47:24,260 And you were the ones who had the courage, the foresight 1716 01:47:24,260 --> 01:47:26,420 and, really, the selflessness to say, 1717 01:47:26,420 --> 01:47:30,140 "Yes, I am going to volunteer for this mission and I do not know 1718 01:47:30,140 --> 01:47:32,020 "what's on the other side." 1719 01:47:33,300 --> 01:47:37,260 We do not know what Pfizer will do, but we will leave no stone unturned 1720 01:47:37,260 --> 01:47:39,820 until we succeed, because succeed we must 1721 01:47:39,820 --> 01:47:42,940 on behalf of the ten million-odd Parkinson's sufferers in the world. 1722 01:47:42,940 --> 01:47:44,580 So, thank you, and God bless. 1723 01:47:46,340 --> 01:47:49,980 After five years, 42 ground-breaking surgeries 1724 01:47:49,980 --> 01:47:52,420 and over 1,000 infusions 1725 01:47:52,420 --> 01:47:56,180 the £3 million trial is over... 1726 01:47:57,580 --> 01:48:01,100 ..and everything now depends on what Pfizer does next. 1727 01:48:09,220 --> 01:48:11,500 Three months after the event, 1728 01:48:11,500 --> 01:48:14,340 Tom wakes up in the middle of the night, in pain. 1729 01:48:15,580 --> 01:48:19,820 About four o'clock in the morning, on the Wednesday morning, Tom... 1730 01:48:19,820 --> 01:48:21,580 SHE SOBS 1731 01:48:23,860 --> 01:48:25,740 He woke up, shouting. 1732 01:48:28,100 --> 01:48:30,220 And I said, Tom I need to call an ambulance." 1733 01:48:30,220 --> 01:48:32,220 And he said, "No, I'm OK." 1734 01:48:32,220 --> 01:48:33,660 And I said, "You're not OK." 1735 01:48:37,500 --> 01:48:41,860 He was doing all sorts of jokes with this lovely lady paramedic 1736 01:48:41,860 --> 01:48:44,900 and I thought, "Oh, OK, you're not too bad." 1737 01:48:47,100 --> 01:48:50,740 And then, his head had gone down and he wasn't responding. 1738 01:48:50,740 --> 01:48:52,900 And I was just sort of saying, "Tom, Tom," 1739 01:48:52,900 --> 01:48:54,340 and he wasn't responding to me, 1740 01:48:54,340 --> 01:48:55,860 and they got him on a chair thing 1741 01:48:55,860 --> 01:48:58,420 and took him downstairs, shut the doors of the van 1742 01:48:58,420 --> 01:48:59,900 and started to work on him. 1743 01:48:59,900 --> 01:49:03,300 And I can remember sitting on the steps with the door open, 1744 01:49:03,300 --> 01:49:05,340 watching it, thinking, "You don't die. 1745 01:49:05,340 --> 01:49:07,020 "Tom, you don't... What?" 1746 01:49:07,020 --> 01:49:10,700 Cos I could hear the defib being zapped 1747 01:49:10,700 --> 01:49:15,660 and you could see the movement of them doing CPR in the van. 1748 01:49:15,660 --> 01:49:18,540 Tom is taken to hospital... 1749 01:49:18,540 --> 01:49:20,540 ..where he's pronounced dead. 1750 01:49:23,700 --> 01:49:26,260 One of the paramedics came up to me and said, 1751 01:49:26,260 --> 01:49:28,100 "He wouldn't have known anything." 1752 01:49:28,100 --> 01:49:30,900 He didn't know a thing. So that's a nice way to go. 1753 01:49:39,060 --> 01:49:42,500 His mother said, when she came to see him, 1754 01:49:42,500 --> 01:49:46,100 that she'd forgotten that he could be still. 1755 01:49:49,180 --> 01:49:51,380 Cos he moved around so much near the end. 1756 01:49:55,740 --> 01:49:59,420 A postmortem reveals that Tom died of myocarditis, 1757 01:49:59,420 --> 01:50:03,580 a heart condition unrelated to Tom's Parkinson's, 1758 01:50:03,580 --> 01:50:06,180 or the trial, that can kill without warning. 1759 01:50:08,100 --> 01:50:10,940 It was a total shock, and awful... 1760 01:50:13,580 --> 01:50:17,860 ..cos Thomas is so central to everything we've done. 1761 01:50:17,860 --> 01:50:21,100 And, you know, he drove me on and he was a friend 1762 01:50:21,100 --> 01:50:22,820 and I loved his company. 1763 01:50:22,820 --> 01:50:25,780 You know, I loved being with him and so on. 1764 01:50:25,780 --> 01:50:28,980 It was, without doubt, the worst point, for me, 1765 01:50:28,980 --> 01:50:30,820 of the whole experience. 1766 01:50:30,820 --> 01:50:33,460 I would have liked to have... 1767 01:50:33,460 --> 01:50:34,860 ..done better for him. 1768 01:50:36,540 --> 01:50:38,060 So... 1769 01:50:38,060 --> 01:50:41,780 I know he had a tough time through the whole thing. 1770 01:50:41,780 --> 01:50:43,460 HE SIGHS 1771 01:50:43,460 --> 01:50:44,540 Yeah. 1772 01:50:50,100 --> 01:50:53,060 But first, news that the pharmaceutical giant Pfizer 1773 01:50:53,060 --> 01:50:56,460 has pulled out of research into neurodegenerative diseases 1774 01:50:56,460 --> 01:50:58,260 like Alzheimer's and Parkinson's. 1775 01:50:58,260 --> 01:51:02,100 In January 2018, Pfizer announces it's closing its 1776 01:51:02,100 --> 01:51:03,940 neuroscience research division. 1777 01:51:05,420 --> 01:51:10,060 The volunteers are told the company has dropped GDNF. 1778 01:51:10,060 --> 01:51:12,740 In reality, progress has been worryingly slow. 1779 01:51:12,740 --> 01:51:14,460 Over the last 15 years, 1780 01:51:14,460 --> 01:51:18,180 nearly every trial into new treatments has ended in failure. 1781 01:51:18,180 --> 01:51:22,220 And Pfizer's unlikely to be the only company to say, "Enough is enough." 1782 01:51:24,740 --> 01:51:28,340 The medical world, the scientific world, the Parkinson's world 1783 01:51:28,340 --> 01:51:30,580 has just written it off as if we're a load of idiots 1784 01:51:30,580 --> 01:51:31,980 who've just been done over. 1785 01:51:34,580 --> 01:51:37,540 And I want to scream, because I know this stuff works. 1786 01:51:37,540 --> 01:51:41,540 And I keep hearing Tom's voice all the time - all the time - 1787 01:51:41,540 --> 01:51:45,260 in my ear, going, "Go on, Vicki. Go on. Do something." 1788 01:51:46,420 --> 01:51:47,940 I don't quite know what to do, 1789 01:51:47,940 --> 01:51:51,980 I don't know quite how I'm going to do it... 1790 01:51:51,980 --> 01:51:54,500 ..but I sure as hell know I'm not going to just sit here 1791 01:51:54,500 --> 01:51:56,540 and do nothing, and lay down and bloody die. 1792 01:52:01,220 --> 01:52:03,500 I found it incredible. 1793 01:52:03,500 --> 01:52:08,540 And they, just with a sweep of a pen, get rid of a whole division. 1794 01:52:10,340 --> 01:52:14,780 Pfizer maintains the move will ultimately benefit neuroscience 1795 01:52:14,780 --> 01:52:17,300 by freeing up money to invest in other companies' 1796 01:52:17,300 --> 01:52:19,420 more successful research efforts. 1797 01:52:20,820 --> 01:52:23,780 Of course, there have to be commercial decisions. 1798 01:52:23,780 --> 01:52:25,860 But, you know, this is a big one. 1799 01:52:25,860 --> 01:52:29,300 The impact is huge on everybody here. 1800 01:52:29,300 --> 01:52:31,900 We all put our necks on the line to prove, one way or another, 1801 01:52:31,900 --> 01:52:34,540 whether GDNF worked or not. 1802 01:52:34,540 --> 01:52:37,020 And here we are, five years later, 1803 01:52:37,020 --> 01:52:40,020 with bits of metal and plastic in our brains. 1804 01:52:42,460 --> 01:52:44,300 And we don't know. 1805 01:52:44,300 --> 01:52:48,340 The greatest thing the trial provided me was hope. 1806 01:52:48,340 --> 01:52:49,780 And that's... 1807 01:52:49,780 --> 01:52:51,660 ..gone. 1808 01:52:51,660 --> 01:52:53,860 Why do WE do it? 1809 01:52:53,860 --> 01:52:55,460 We want to live longer. 1810 01:52:55,460 --> 01:52:59,100 That's the truth. 1811 01:52:59,100 --> 01:53:00,660 They do it for money. 1812 01:53:02,980 --> 01:53:04,660 I've got to got to the clinic again. 1813 01:53:04,660 --> 01:53:06,580 VOICEOVER: I'm willing to sacrifice. 1814 01:53:08,100 --> 01:53:09,900 You're not. 1815 01:53:09,900 --> 01:53:11,700 You just want to be paid. 1816 01:53:14,140 --> 01:53:15,420 It felt as if we were part 1817 01:53:15,420 --> 01:53:18,020 of something really, really ground-breaking. 1818 01:53:18,020 --> 01:53:20,860 But, you know, that's all come to an end. 1819 01:53:22,700 --> 01:53:25,740 VOICEOVER: It's as if you're of no consequence, 1820 01:53:25,740 --> 01:53:27,580 got no say in it at all. 1821 01:53:27,580 --> 01:53:31,660 After all the time and effort that people put into it. 1822 01:53:40,980 --> 01:53:45,220 It's now two years since Nick had his last infusion. 1823 01:53:47,860 --> 01:53:50,860 Almost all the volunteers want GDNF back. 1824 01:53:52,260 --> 01:53:55,580 But the trial results leave the scientific world divided. 1825 01:53:55,580 --> 01:53:57,460 Lamb's-ears. 1826 01:53:57,460 --> 01:54:00,460 The improvements in the second nine months could have been down 1827 01:54:00,460 --> 01:54:03,620 to a long-lasting placebo effect 1828 01:54:03,620 --> 01:54:07,980 and it's the second time GDNF has failed in a high-profile trial. 1829 01:54:07,980 --> 01:54:11,060 It's been eaten a bit by the caterpillar. 1830 01:54:11,060 --> 01:54:14,100 DR WHONE: It wouldn't be the first drug that's failed 1831 01:54:14,100 --> 01:54:17,340 in clinical trials and then come good, by any means. 1832 01:54:17,340 --> 01:54:18,820 Just give us a tug, Albert. 1833 01:54:18,820 --> 01:54:20,140 Oh, yeah, sure. 1834 01:54:22,580 --> 01:54:25,660 Often, it is a question of having to go at something a number 1835 01:54:25,660 --> 01:54:28,940 of times, and each time you refine the way you do it and how you do 1836 01:54:28,940 --> 01:54:33,180 it and to whom you do it. And, eventually, you may get there. 1837 01:54:33,180 --> 01:54:35,540 Yee-haw! 1838 01:54:35,540 --> 01:54:38,140 Although you do have to make a decision sometimes 1839 01:54:38,140 --> 01:54:40,900 that this, for whatever reason, isn't going to work 1840 01:54:40,900 --> 01:54:44,740 and you're better off putting your efforts into another area. 1841 01:54:47,820 --> 01:54:50,060 INDISTINCT 1842 01:54:50,060 --> 01:54:51,740 I know the drug works. 1843 01:54:53,060 --> 01:54:55,300 So where do we go from here? 1844 01:54:55,300 --> 01:54:57,180 It has to be a dose issue. 1845 01:54:58,580 --> 01:55:00,380 SHE LAUGHS 1846 01:55:00,380 --> 01:55:03,620 We've got ginger ones, chocolate ones, 1847 01:55:03,620 --> 01:55:05,060 mint chocolate ones... 1848 01:55:05,060 --> 01:55:07,340 New toxicology data suggests 1849 01:55:07,340 --> 01:55:10,780 it would be safe to increase the dose fourfold. 1850 01:55:10,780 --> 01:55:13,180 And we're busy trying to wave the Parkie flag, 1851 01:55:13,180 --> 01:55:14,740 cos we need the money for research. 1852 01:55:14,740 --> 01:55:18,100 So, if you'd like to buy a tombola ticket, they're a quid. 1853 01:55:18,100 --> 01:55:21,780 MedGenesis is now trying to raise the money needed 1854 01:55:21,780 --> 01:55:23,580 for a phase three trial. 1855 01:55:25,620 --> 01:55:29,660 Both the US and European drug regulatory bodies 1856 01:55:29,660 --> 01:55:32,700 say they would welcome an application for a further trial 1857 01:55:32,700 --> 01:55:34,540 if the money can be raised. 1858 01:55:35,540 --> 01:55:38,820 I'm hopeful that MedGenesis will raise the money 1859 01:55:38,820 --> 01:55:41,220 short shrift and we'll be back on track. 1860 01:55:59,940 --> 01:56:04,780 Every hour, two people in the UK are diagnosed with Parkinson's. 1861 01:56:04,780 --> 01:56:06,980 That is only going to progress. 1862 01:56:09,260 --> 01:56:11,780 Being a part of the GDNF trial 1863 01:56:11,780 --> 01:56:16,780 was so inspiring and gave Tom huge hope, huge hope for the future. 1864 01:56:20,020 --> 01:56:24,260 This has only been impossible by enormous courage of the patients. 1865 01:56:26,740 --> 01:56:31,300 We now have a means of safely delivering drugs into the brain. 1866 01:56:31,300 --> 01:56:36,900 So the contribution that everybody's made to just taking the technology 1867 01:56:36,900 --> 01:56:40,700 forward will have a huge effect on so many people in the future. 1868 01:56:44,620 --> 01:56:47,140 All the time, when you're doing clinical research, 1869 01:56:47,140 --> 01:56:49,700 as long as you do it well, you can learn something 1870 01:56:49,700 --> 01:56:52,900 and it's a bit like putting another brick in the wall. 1871 01:56:53,980 --> 01:56:56,420 And, eventually, something will give. 1872 01:56:58,860 --> 01:57:01,860 These diseases aren't just bad for the people that have them 1873 01:57:01,860 --> 01:57:05,340 they're very difficult and damaging to families and friends. 1874 01:57:05,340 --> 01:57:08,380 And you either accept that and say, "Well, that's the status quo, 1875 01:57:08,380 --> 01:57:11,420 "we can't do any more," or we have to keep trying.