Sonia Gandhi's mission to change Parkinson's trials

If you ever feel depressed about anything from the slow progress in the hunt for a cure for Parkinson’s to the state of British science I have a suggestion. Take a train to London’s St Pancras and walk out of the station on the west side and across the road into the airy glass palace that houses the Francis Crick Institute.

That is what I did the other day, expecting maybe a 45 minute briefing on some quite obscure work on Parkinson’s being done at the biomedical research institute. Instead, I emerged after two and a half hours, my head spinning with all I had learned and convinced that the team I had met could play a major role in uncovering the mechanisms behind the world’s fastest growing neurological condition.

Professor Sonia Gandhi at the Francis Crick Institute

My guide was Professor Sonia Gandhi, a neurologist seeing patients at the Queen Square National Hospital for Neurology two days a week, an academic leading a team exploring what Parkinson’s does to the brain the rest of the time. Professor Gandhi is one of those rare scientists both hugely enthusiastic about explaining their work and with the skills to make it comprehensible.

As she took me on a journey deep into the brain, first in her office, then in the labs where ultra powerful microscopes zeroed in on single cells, I just about managed to keep up, both literally and figuratively. I am going to write something looking in more depth about how far Professor Gandhi and her team have got in undertsanding the Parkinson’s brain, but first I want to talk about something more likely to deliver hope in the short-term for those of us with the condition.

Often it seems there is a huge gulf between the teams on the ground running clinical trials for promising drugs and the scientists in their labs pursuing blue sky research projects that last for years and may never deliver practical treatments. But at the Francis Crick Institute they do both the long-term research and get their hands dirty (ok, that’s a slur) helping with drug trials. Professor Gandhi leads a reserach team at UCL which is involved in the ambroxol and exenatide trials, looking into what these promising drugs actually do inside the brain.

But what she has seen of the lengthy trial process for Parkinson’s drugs has made the professor determined to change things:

“The way that trials are done at the moment is deeply inefficient. So you have a phase two trial. It all gets dismantled - the trial machinery, the centres that delivering it - and you get a big gap. And then you have a phase three trial. And then it ends in failure.”

Then she shows me a depressing chart illustrating the progress of potentially disease modifying drugs through trials over the last 25 years:

“They've all ended in failure. But they've ended in failure after approximately 10 to 15 years.”

She believes the answer is something called ACT PD (Advanced Clinical Trials in Parkinson’s), an initiative set up by a group of academic clinicians - people who, like her, work at both Queen Square and UCLH, and also across the UK in centres in Plymouth and Newcastle.

Instead of building a massive costly trial infrastructure around one drug trial and then scrapping it- which she compares with building a huge stadium for one tournament and then dismantling it - the idea is to build a multi-arm system with many drugs being tested at once. “You have one control , and four or five drug arms. You run them all together and then you do what's called an interim analysis and anything that's not positive you just drop out and take on a new drug." There are no gaps and the trial machinery remains in place.

And the project has big ambitions:

“In this programme we have 50 centres across the UK - they'll all be trial ready. And then we just keep trialing drug after drug after drug until a disease modifying therapy is found.”

The idea that the long-awaited drug which will finally have a real impact on the progression of Parkinson’s could be born in the UK is very exciting - especially given recent depressing news about clinical trials here. In February the senior clinician Sir John Bell warned that patients faced missing out on cutting edge dementia and cancer treatments after a report showed the UK had fallen from fourth to tenth place as a home for phase 3 trials.

Sir John said the burea8ucracy that makes trials so slow and had been swept away during the pandemic but. was now returning. Yet Sonia Gandhi says the NHS should make the UK a very attractive home for trials:

"The UK is a very cost effective place to do trials. And you can't do multi arm trials in many places because you need everybody on a centralised healthcare system, such as the NHS, and you also need to have clinical research embedded in the NHS . Which is why the UK did very well in terms of trials and advances in biomedicine in the pandemic."

But she has a message for policymakers about what is at stake:

“We are at a tipping point, it is the perfect storm at the moment in terms of both getting the trials right, and getting the science right,. Doing really disruptive and paradigm shifting science has not been possible always before just because the technologies haven't been there. But we're at a point where we can do that. And at a time when there's huge demand and need from our patients.”

But she makes it clear that it won’t be cheap:

“How do we make that happen? I think it's by bringing the scientists and clinicians together in a very unified way. And I think it's by backing it with with the sort of funds that these type of technologies and trial designs need.”

I can almost hear the Chancellor groaning at another demand for higher spending at a time when everything from crumbling schools to public sector pay deals is putting pressure on the government’s. finances. Yet if ministers are serious about playing to Britain’s strengths in areas such as AI and bioscience then funding scientists like Professor Gandhi and her team will have to be a priority.