Parkinson’s - hope and frustration

Breakthroughs always seem five years away

I spent an inspiring afternoon last week hearing some brilliant scientists who were unusually good communicators explaining their research into new treatments for Parkinson’s. At the Cure Parkinson’s Research Update in the august surroundings of the Royal Society of Medicine we heard about futuristic cell therapies and a promising drug which could be the first to halt the disease in its tracks. But I left in a rather downbeat mood, aware of just how long we may have to wait for that breakthrough which always seems to be five years away.

Take Professor Roger Barker’s presentation about the history of the quest to replace lost dopamine cells by intervening directly in the brain. The Cambridge academic, one of the world’s leading neuroscientists, was an engaging speaker who gave a non-specialist audience a very clear explanation of the science of cell and gene therapy.

But it was a story of hope being inevitably followed by despair - trials which seemed to offer promising results with one set of patients later proving disappointing in another experiment. Since the late 1980s, Professor Barker and colleagues around the world have been refining their techniques, never giving up on the idea that growing dopamine cells and inserting them into people with Parkinson’s could make drugs like Sinemet which many of us currently use obsolete.

But the trials of these techniques only involve s tiny number of people and have proved very lengthy and expensive to conduct. A 2019 study of trials involving stem cells found they had had very mixed results - ‘the outcomes…..have been variable with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects,”

Professor Barker told the audience that translating what at first seemed major advances into practical treatments remained challenging: “we have enormous problems in trying to translate from the lab to the clinic.”

The same seems true of pharmacological routes to confronting Parkinson’s but at least for one drug the road seems to be getting shorter. Ambroxol, the simple cough medicine which could be the first drug to slow the progression of the disease, is now going to have a phase 3 trial, the last stage before it can be prescribed by doctors. The audience at the Cure Parkinson’s seminar was told about innovations in clinical trials, such as multiarm, multistage trials already commonly used in testing cancer drugs.

This approach means that a patient can swiftly be switched to another trial drug if the one they start with proves ineffective. Nevertheless we also heard that recruiting the 330 people needed for the Ambroxol trial would probably take two years which seems an extraordinarily long time given that the phase 2 trial results were published in 2019 and the audience was full of people eager to participate. The problem is that there is no straightforward way of getting a message to all 145,000 people with Parkinson’s in the UK. A national database would be a great idea but I suppose there would be objections from privacy campaigners.

The sheer dogged persistence of Professor Barker and the other researchers we heard from at the event is admirable but for those waiting for good news it is frustrating to be told once again that it may be five years away.

At the q and a session at the end of the event one woman surely spoke for many: “Can we just make a call for a bit more urgency because we are deteriorating all the time? We haven't found anything since the 1960s that slows or stops it.” She also made it clear that she had not set her sights on a cure:" “The most I'm hoping for is something that slows it down a bit in my lifetime so I've got more hope.”

And perhaps our best hope is for a treatment which can make our lives a little easier. A few days before the Cure Parkinson’s Research Update I had a chat with Kathy Abram and her husband Tom who wanted to tell me about a drug which could deal with one of the most distressing symptoms, freezing of gait and falls.

Kathy, who was diagnosed in 2008, told me she now walks with a stick in one hand while holding on to Tom with the other, but often she just freezes: “We could be walking very well, but I have a problem, I stop and then I can't start again.” This threatens to be very disabling so the couple were interested when they learned about a drug that could help.

The only problem was that Rivastigmine was a drug for people with Alzheimer’s - and Kathy would have to pretend she had dementia to get it prescribed. Now though there is a major clinical trial which goes by the name of CHIEF-PD, the Cholinesterase Inhibitors to Prevent Falls in Parkinson’s Trial. It will look at a number of drugs like Rivastigmine which are known as Cholinesterase Inhibitors and are currently used to treat people with memory problems.

Kathy has just been through a three hour interview, the start of her participation in the CHIEF trial which aims to recruit 600 people. She knows that there is no guarantee that the drug will work, that she will be given it rather than a placebo, or that if it is shown to be effective she will quickly be prescribed it at the end of the trial.

When I put all these uncertainties to her, however, she simply said “But it would be so wonderful if it did work.”

The one other thing I took away from the Cure Parkinson’s event was that we should not be sniffy about the placebo effect - if something makes you feel better, then that’s a real gain. And one of the most powerful placebos is hope.