‘Give me back my miracle’: is this the cure for Parkinson’s?
The trial of a promising treatment may have ended in disappointment, but the people whose lives it changed have hope for the future
Bryn Williams was just 36 when he noticed a small tremor in his right arm. A successful patent attorney, the father of two found himself pressing the wrong button on his computer mouse at work, accidentally deleting whole paragraphs.
He visited his local GP and, after a long series of tests, was diagnosed with early onset Parkinson’s disease. The degenerative disorder usually affects older people: fewer than 5% of patients are diagnosed before their 40th birthday.
Williams, who had driven his daughter to her first day of school the day before his diagnosis, couldn’t help feeling hard done by. “It was just horrendous,” Williams, now 47, remembers. “I didn’t know anything about the disease, I didn’t know if I was going to die. [I remember thinking] how are you going to support your family? How are you going to live? Are you going to get kicked out of your house? Are you going to lose your job? It was just a spiral for about two weeks.”
There is no cure for the condition, which affects one in every 350 British adults, and drug treatments – the most common of which is levodopa – can only slow the gradual creep of tremors, stiffness and slowness of movement that eventually leaves sufferers wheelchair- or bed-bound.
Williams couldn’t bear to think of his future with the disease: “Looking at the bare facts, I’ve seen people with Parkinson’s who are 10 years further down the line than I am, and they’ve got no life at all.”
Which is why, seven years ago, he decided to join a highly experimental medical trial to test a new treatment lauded by some as a “miracle”. The 18-month, £3m experiment, carried out on 41 patients at Frenchay and Southmead hospitals in Bristol, centred on a naturally occurring protein called Glial Cell Line Derived Neurotrophic Factor (GDNF). Researchers believe GDNF can regenerate the dopamine-producing brain cells that are gradually destroyed by Parkinson’s, thereby reversing the condition – something no other treatment can do.
Previous work on GDNF has proven difficult because, when taken as a pill or injected into the bloodstream, it cannot break across the brain’s defensive barrier. But in this study, for the first time, robot-assisted neurosurgery bypassed the barrier entirely by drilling ports directly into the patients’ skulls, to allow the drug to be administered precisely into the affected areas of their brain in 10 monthly infusions over a nine-month period.
Initial signs were little short of incredible.
Assessed in a laboratory every eight weeks, many of the patients saw dramatic improvements to their symptoms, as chronicled in a new BBC documentary, The Parkinson’s Drug Trial: A Miracle Cure? They were able to rotate their hands without shaking, and could walk across a room without assistance. Some reported feeling “100% better”.
But it was outside the bright lights of the doctor’s office where patients saw the real difference. Some were able to dress themselves without any help. Others could walk their dogs or jog around their local park for the first time in years. One participant, 47-year-old Vicki Dillon, described the treatment as “a bloody miracle”.
And that is what made last week’s news so disappointing.
On Wednesday, a report published in the Journal of Parkinson’s Disease concluded that the experiment had not met its strict target set by regulators. For the first nine months of the trial, half of the patients were chosen at random to receive a placebo infusion – none of the patients, nor the doctors, knew which. But for GDNF to be considered effective, those who received the drug had to show improvements in symptoms that were 20% better than those given the placebo. No such luck, according to Wednesday’s report; the uptick was just 6%.
It is particularly frustrating for Williams, who was on the dummy infusion for the first nine months of the trial, experiencing a brief boost that faded away after a few months. All 41 patients then underwent an extension phase, during which they each received GDNF for a further nine months: “It wasn’t considered ethical to put people through brain surgery without ever giving them a chance to have the drug,” explained Dr Alan Whone, the principal investigator. The difference, for Williams, was immediate.
“More than anything, there was a continual improvement in the fluidity of my movement,” he remembers. “I was back running again, and it was just a wonderful feeling. I could go for a five- or six-mile run and not suffer foot cramps. People said I used to walk with a stoop before the trial, and now I was walking upright, striding out.”
It gave succour to his and his wife Victoria’s long-held hope that he will one day walk their two daughters up the aisle on their wedding days. “It gave me confidence for the future. The trial was genuine hope. It wasn’t hope I’d invented, it wasn’t hope I’d designed, it wasn’t hope I’d made myself. It was real, scientific hope, and that’s the most powerful thing.”
Nick Vallotton, 45, a father of three who lives with his partner Sally, also witnessed “spectacular” changes to his condition. He was diagnosed with Parkinson’s at 38 when, during a nursing shift at his accident and emergency department in Gloucestershire Royal Hospital, he noticed a sharp pain in his shoulder. Like Williams, he unknowingly spent the first nine months of the trial on the placebo, but when he finally received GDNF, noticed dramatic improvements.
“Physically, I felt different. I got my function back in my right hand – before, I could hardly write – and I could eat properly. My voice was a massive thing; lots of people with Parkinson’s get very quiet and that’s changed massively.”
Since all patients received GDNF in the second phase and there was no placebo to compare it to, evidence of improvement was deemed scientifically inconclusive. Neither of the men have been allowed the drug since the trial finished two years ago, and much of their hard-won progress is fading away. Vallotton is finding it more difficult to move, and says the dreaded “stiffness and slowness” is gradually returning. “The frustration is the killer.” Before his diagnosis, “I could go walking up in the Alps. I was dexterous enough to stitch people up in the emergency department. I could do whatever I needed. And now I have to pre-plan, and think ‘When are my tablets going to wear off?’, ‘Am I going to be able to do this?’”
These everyday difficulties are all the more painful after the GDNF trial showed him there could be another way: “Parkinson’s, in a nutshell, is a complete waste of my time, because I’ve got so much to do. I’ve got 20 years left of work, I’ve got small children, stepchildren, houses to do up, kitchens to fit. I’ve just got too much to do to waste my time stumbling about.”
Williams, too, has found his symptoms worsening since coming off the drug. He has maintained his career as a patent attorney, but now spends an hour each day “sitting in my chair, not really functioning very well” after his daily dose of levodopa has worn off.
Professor Steven Gill, the neurosurgeon at the helm of the study, admits that the results published on Wednesday were a “a huge disappointment”, but is pleased that GDNF showed enough promise to move onto the next phase of clinical trials. “I know this stuff works,” he says. “It’s a question of how can you deliver this to huge populations of patients at the right dose, at the right time? What matters is getting to the next step.”
Although his year of physical freedom has come to an end, Williams remains optimistic that he will find a way of returning to his “miracle” treatment: “There’s a sunrise waiting to happen and it’s not far away.”
– © The Sunday Telegraph