Patience and Parkinson's

A long wait for a wonder drug

When will it be goodbye Sinemet, hello wonder drug?

This week I spent a day mostly devoted to Parkinson’s Disease, its past, present and future. In the morning I headed to the hospital for an appointment with my neurologist, an important occasion, as anyone with this condition will tell you, because you can wait many months for such meetings. 

It turned out to be an excellent encounter with not one but two doctors, both sharing an interest in research and acting as a kind of tag team. We talked at length about my symptoms, the current thinking about everything from deep brain stimulation to wearables that can monitor the condition- I even showed them the TikTok I’d made about skiing with Parkinson’s as a demonstration of how my balance had been affected by the disease. 

Then there was what you might call the “practical”. They made me walk up and down the corridor outside their office, stood behind me and jerked my shoulders backwards, laid me on a bed and pulled and stretched my limbs in every conceivable direction - “we neurologists are so cruel” they joked. 

Their verdict was that I was doing okay but could perhaps do with a top up of my medication to help with an insomnia problem which could be partly a symptom of my Parkinson’s. I was given a prescription for some slow release Sinemet, to be taken last thing at night, then at lunchtime. 

I emerged very satisfied by the care and attention shown by the doctors but aware of what a low-tech experience it had been and how little the treatment of Parkinson’s has moved on. Analysis of the symptoms and how they are developing is still dependent on the patient’s recall and the doctor’s observations on the day and treatments such as Sinemet are upgraded forms of L-Dopa, the drug discovered 60 years ago.

But that afternoon, I got an intriguing glimpse of the future at a conference held by Cure Parkinson’s, a charity with a singular focus on funding research which might finally provide a new breakthrough in treatment of the disease.

The conference itself was tightly focused on one area of research - the links between Type 2 diabetes and Parkinson’s and trials to see whether drugs which were used to treat diabetes might also be effective for people with the neurodegenerative disease.

We had very detailed presentations from the neurologists running trials for two drugs, exenatide and liraglutide. Both are what are known as GLP-1 agonists, drugs which mimic a type of hormone to stimulate the release of insulin. But there is evidence that they can improve brain function too, rewiring the connections that keep dopamine flowing.

Liraglutide is the more advanced drug but exenatide is much further down the research path. Several people in the conference room had been on one of the trials and there was a palpable sense of excitement as some very positive results were explained in a series of. charts.

The driving force behind this project has been Cure Parkinson’s research director Dr Richard Wyse. He first spotted the potential of these diabetes drugs back in 2010 and started trying to cajole some leading neurologists into conducting a trial.

He succeeded and the results astonished him, in that for the first time a drug seemed to halt the progression of the disease:”There’d been nothing like it before - it appeared to slow disease progression in the first six months, and that was maintained at the one year point.”

To be clear, existing medication such as the Sinemet I take, ameliorate the symptoms of Parkinson’s but don’t slow the progression of the disease, so this was a major breakthrough.

But a phase 1 trial with no placebo drug as a comparison was just the beginning, Going further meant raising a lot more money and fortunately the Michael J. Fox saw the value in funding a stage 2 trial.

The results of that were published in 2017 and were so impressive that. Cure Parkinson’s began to talk of when not if the objective in its name was achieved. That may have been premature - to get a drug approved for prescription by doctors a Phase 3 trial was needed.

Recruitment for that began in 2019, was slowed down by the pandemic and results will not be available before 2024. That may seem a long time when you consider just how rapidly a Covid vaccine was tested and approved but Dr Wyse points out that a slow degenerative disease presents a very different problem - one of measurement.

If people with Parkinson’s see their health decline by just 4% a year then it will probably be several years before there is an appreciable difference between those given the drug and those given the placebo. (By the way, the good news is that Richard Wyse and others are working on a new way of measuring the progression of Parkinson’s which I will write about later.)

And Dr Wyse strikes another cautionary note - exenatide only delivers a strong response in about 40% of patients and there is work to be done to find out what the difference is between them and the other 60%. Without that data, doctors may be reluctant to prescribe the. drug even once it has cleared all the regulatory hurdles.

So the lesson I took from the day is that there is hope that a breakthrough is coming - but that endless patience is the main virtue required of anyone with Parkinson’s.