Movers and Shakers: Cell Therapy

Roger Barker's four decade quest to cure Parkinson's

In the course of recording forty episodes of Movers and Shakers - yes, that’s the milestone we reached this week - we’ve met some brilliant doctors and scientists. But I don’t think any of them has kept us quite so gripped as this week’s guest Roger Barker. As the Cambridge University professor of neuroscience took us through a quest stretching back to the 1980s to use cell therapy to slow, stop or reverse Parkinson’s he reminded me of Monty Python’s Black Knight.

Just as the knight would dismiss every lost limb as “merely a flesh wound”, Professor Barker treated every failed trial or funding crisis for cell therapy as just another temporary setback on the road to certain victory.

He started by explaining the basic idea behind cell therapy in Parkinson’s - replacing lost dopamine cells in the brain. We start with half a million of these:

“When you lose half of those you develop the first clinical features of it - if you put back that number of cells, in theory you should be able to return people back to what they were like before they first developed their Parkinson's.”

That seems simple until you consider several big challenges - getting hold of the cells and injecting them safely into the brain. But in the late 1980s Roger Barker saw what was going on in Sweden, where clinical trials were underway, and came to a life-changing decision. “It was clear that this therapy was intuitively an obvious thing to try and it was starting to look quite successful. So it was on that background that I decided that I would get involved with brain repair and trying to put cells into brains to repair circuits that were misbehaving.”

Why Sweden rather than the US? The answer lies in the politics of abortion. The cells used came from aborted foetuses and at that time it was impossible to get government funding for such research in the United States.

Those early Swedish trials were of a small scale, involving 17 participants, and did not conclusively prove the case for cell therapy but for two British patients who travelled to Sweden to take part the results were amazing: “30 years after they had their transplant, they were on no medication, they had a motor score on a standard scale that was less than when they presented to their neurologist 30 years previously - for these patients it was transformative.”

Professor Barker is reluctant to call it a cure but to us this sounds miraculous and he agrees that for all intents and purposes these two people were cured.

Then when Bill Clinton was elected US President in 1992 he moved to allow funding for the use of foetal tissue in research - and, paradoxically, that is when things began to go wrong for cell therapy. “The trials weren't as well conceived as one might like. Now, a consequence of this was when those trials published their results in 2001 and 2003 they didn't produce a clinical benefit.”

One problem was that these were randomised control trials. As Roger Barker puts it, imagine Rory is sent into the operating theatre, has a hole drilled in my head and cells inserted, whereas the same thing happens to Jeremy except after drilling the hole in his head the surgical team sit around twiddling their thumbs for hours and it is only five years later that we and the scientists running the trial find out that I’ve had the cells and Jeremy has received the placebo. Not a very attractive proposition for trial participants. (We discuss how many medical advances have happened without such a process - there were no randomised control trials before the first heart transplant and Dr Christiaan Barnard’s patient died just 18 days after the operation.)

There were other issues with the design of the American trials but the end result was that Professor Barker and other cell therapy researchers found it very hard to get funding. By now under the George W. Bush administration the political tide had turned against this kind of research again, and with DBS (Deep Brain Stimulation) taking off, there was a feeling that cell therapy was a failed experiment when there were more practical alternatives.

But Roger wasn’t giving up. He tells us about the advice he gives to young scientists: “Wherever you're doing your research, just stick at what you're doing and at some point it will be flavour of the month.”

He convened a conference in London to re-examine the findings of all the trials carried out so far, and work out why some patients had done well, others had not: “The critical thing seemed to be the age of the person having the transplant, how advanced they were, how long they were followed up, and how much immunotherapy they were given and how much tissue was implanted. So we thought all of these were tractable issues which we could put into a trial.”

Armed with initial funding from the Michael J. Fox foundation and then from the European Union a new round of trials got underway in a spirit of optimism - after all if even just two patients had been shown to experience miraculous and long-lasting improvements after cell therapy, surely the concept had been proven?

But here’s the news that will have every Parky groaning - the trials started in 2010 and fourteen years later are still ongoing. All sorts of practical and regulatory challenges have slowed things down but the most intractable issue has been getting hold of enough embryonic cells to transplant - Roger Barker says over a three year period from 2015 to 2018 his team managed 21 transplants for 11 patients, but had 87 operations cancelled due to a lack of foetal tissue.

But what has brought new hope are a series of dramatic scientific advances, notably the 2007 demonstration by the Japanese Nobel Prize winner Shinya Yamanaka that it was possible to take any human adult skin or blood cell and program it to look like an embryonic stem cell. Five years later two studies showed you could take those cells and reprogram them into dopamine cells.

Turning lab experiments into clinical practice and proving that injecting these cells into brains is safe is a very long and expensive business but finally trials are underway using this new approach to cell therapy. Roger Barker is running one of these trials with the backing of the pharmaceuticals giant Novo Nordisk.

The fact that big pharma is now involved gives him confidence that this time we will find out whether cell therapy is the answer to the quest to end Parkinson’s or another blind allley: “If the trials are proving too difficult, they'll pull the plug. If they're working, then they're already thinking about their marketing trials to get it to market.”

We end the episode hugely impressed with Roger Barker’s continued faith in what he sees as a future where newly diagnosed Parkinson’s patients are offered a treatment which stops the disease in its tracks and means they never need any further medication. Even Jeremy Paxman is won round:”I thought he was persuasive,” he says.”I was very, very impressed.”

Sadly, none of us expects this Parkinson’s breakthrough to happen in our lifetime, but as Mark Mardell says, “it would be pretty bloody great if nobody else had to get it.”