Movers and Shakers: Enzyme Blockers
Has the judge found a wonder drug?
The judge - or The Honourable Sir Nicholas Mostyn as I suppose I should call him - is a remarkable man. When I first met him, having been told by his friend Edward Stourton that he was in a bad way, having just been diagnosed with Parkinson’s, I was surprised to find him extraordinarily upbeat and positive.
Sure, he was suffering from a number of nasty symptoms of his condition, but he wasn’t going to let this blasted illness beat him. Instead, the man dubbed ‘Tigger’ as a young barrister, set about assembling what he called a support bubble of fellow Parkies in a Notting Hill pub, and then badgered us into starting a podcast.
Three years on from our first meeting, Nick seems as chipper as ever - and with good reason. While my Parkinson’s symptoms have got quite a bit more pronounced over the last eighteen months - and that is probably the case for the other Movers and Shakers - the judge seems, if anything, to be in a better state. Sometimes, I tease him by suggesting that he doesn’t have Parkinson’s at all - he just always wanted to have a hit podcast.
He does confirm that, with the notable exception of the violent nightmares which are a trial for both him and his wife, he is mostly free of the symptoms he had when we met. And he puts it all down to a wonder drug, an enzyme blocker called Opicopone.
When he suggested we make an entire episode about this class of drug, I was dubious - wasn’t it going to be a bit arcane, too specialised to inflict on our audience for half an hour? I turned out to be wrong, mainly because our guest Professor Peter Jenner - “top guru in pharmacology in the country” as the judge introduces him - told us such a compelling story.
First of all he revealed that if we were on the main drug for Parkinson’s levodopa we were already taking enzyme blockers. This was because when levodopa was first introduced it was found that an enzyme broke down the dopamine in the drug before it could get to the brain, making it ineffective:
“The pioneers who introduced levodopa almost gave up because they couldn't get it to work by itself,” he explained. “Even if they gave the patient a tub of it and a spoon to eat it - grams of the stuff were being taken - it didn't work consistently.”
Two drugs companies then discovered that enzyme inhibitors could mute this effect and levodopa, which Professor Jenner told us would never have passed today’s more stringent clinical trials, quickly became the key drug for Parkinson’s.
What we - and Nick - did not understand was why he was taking an extra enzyme blocker. It turns out, though, that things are more complex than we first thought - there is more than one enzyme putting the brakes on dopamine:
“What the judge is now taking is a compound that blocks the other enzyme that also is hammering levodopa,” said the professor. “What they've been trying to do in your case, is to increase the duration of effect of every dose of levodopa by blocking its other router metabolism, by prolonging how long it hangs around in your blood and in your brain.”
He stressed that the enzyme blockers did nothing on their own;
“They are merely there to maximise the efficiency of the gold standard drug for the treatment of the disease. “
Nick Mostyn then outlined the “transformational” effects of opicapone on his symptoms, as measured by his consultant. Which sparked a couple more questions - didn’t this effectively amount to a cure and if so, why weren’t we all going on opicapone?
The answer from the professor was that we are all different in the way our brains absorb dopamine and while the drug worked just about perfectly for the judge, for others it either would not make any difference or would have unpleasant side effects:
“My personal view is we cannot have algorithms for the treatment of Parkinson's disease, where everybody gets treated in the same way,.You have to treat every person as an individual, have personalised focused medicine for each individual, because your response to those drugs is going to be different.”
Personalised medicine is said to be the future, but how quickly that future arrives in an NHS under tremendous strain remains to be seen.
We went on to discuss with another guest, Parkinson’s researcher Lynn Guldin, why the drugs companies were not putting more money into further development of enzyme blockers since they seem to be so promising. She too is puzzled by what appears to be a lack of ambition - but speculates that the drugs just aren’t making enough revenue for them at the moment to spark them into action.
We have a couple of extra items in this episode. First, we discuss my story for this newsletter about complaints about the phase 3 trial for the drug exenatide, hoped to be the first to slow the progress of Parkinson’s. A number of participants in the trial are angry about long delays and ppoor communication from the trial organisers. You can read more about that story here.
And we had what is going to be a regular feature - an update from Gillian Lacer-Solymar about any progress with ourParky Charter. We discussed the “We Will Survive” video and our ambitions for it to bolster the campaign for better Parkinson’s care.
We are now waiting patiently for the Petitions Committee at Westminster to restart the government petitions website - when that happens, we will be seeking 100,000 signatures to a new petition which would spark a debate in Parliament. So, get ready to sign - and in the meantime keep liking and sharing the video!
I was diagnosed with Parkinsons in May 2020. After taking levodopa together with a variety of enzyme inhibitors, in particular entacapone, my symptoms were reasonably well controlled. My condition continued to deteriorate and my quality of life started to suffer as a consequence. Towards the end of 2022 I had developed problems with diarrhoea with all the limitations that brought with it. Following a colonoscopy, I was diagnosis with microscopic colitis. From the Mayo Clinic web page I found a reference which linked taking entacapone and having microscopic colitis. I passed this information on to my consultant who advised that I stopped taking entacapone and assess if this had any basis to it. The diarrhoea stopped almost immediately.
As an alternative I was prescribed opicapone which had only been recently approved by the NHS in Scotland. Sir Nicholas referred in the May 2023 podcast that the introduction of opicapone had made a dramatic difference to him and as your newsletter states ‘transformational effects on his symptoms’. I can concur directly with his view and for me taking opicapone has been a game changer. It had a very positive impact almost immediately. My movement, mobility, energy and enthusiasm for activity, in my case, walking and sea fishing from my boat have become, once more, achievable and enjoyable. More than eighteen months in, these improvements have largely been sustained. I would agree with Sir Nicholas that a whole programme, having a more detailed look at the impact of this drug, could benefit many more Parkinsons sufferers.
Morgan H. Goodlad
Shetland Isles
My brother developed early onset PD 15 almost 16 years ago. Found in the last 4 years that a treatment to address systemic oxidative stress and aggressive management of diet and levadopa to manage symptoms and also to maintain strength has been extremely positive. No progression of the disease 42 months (via PET). UPDRS-III scores are in single digits. Sometimes I think the medical community just expect deterioration.