Why I think the microbiome is key
(Stick with it – links to poo coming up…)
Having been diagnosed with PD, and offered regular Sinemet therapy, I resolved to look for alternatives and hope for a cure. Dopamine – whilst central to PD and effectively the definition of the disease, appears to be only part of the story. In looking for ways to stop the disease progress, it seemed that the “mechanism” itself creates a lot of the symptoms. So addressing the disease process / mechanism protects dopamine neurons (and other bits of the brain) and stops the progress, but also relieves other symptoms and treats the condition directly.
Of interest were (and still are) repurposed drugs. Exanatide, Isradipine, Simvastatin, other glp-1 receptor agonists, Defreraprine. And new drugs – I think the trial I have agreed to is the phase 2 for PX00002 – anyway, it’s a monoclonal alpha synuclein antibody. But these are probably partial solutions, if they work. And they take time to reach authorisation. It looks like Exanatide is now going forward for a phase 3 trial, but that will be 3 years trial duration, so from first intake to last finisher 4 or maybe 5 years. And it hasn’t started yet. And further licencing will be maybe 2 years. If it’s a winner, I could be taking it in 8 years time. But I will have irreversibly lost a lot of neurons in that time.
Isradipine, I can cheat. I have (borderline) hypertension and my UK GP had me on Amlodopine which I blamed for DIP before the DATscan confirmed true (quite advanced) PD. I stopped taking Amlodopine, but my French GP is prepared to prescribe Isradipine. (And my UK GP will prescribe Simvastatin for my high cholesterol). I am a bit statin phobic though
So, back on topic – new drugs aren’t here yet. And, as my reservations about statins affirm, drugs have side effects. So if there are 2 ways to get a result, that are equally effective, a non-drug approach is favourite. (Unless you work for Big Pharma***)
Hopefully – if the disease process / mechanism can be stopped / slowed – then the likes of pluripotent stem cell grafts may restore a more natural dopamine supply (and my guitar playing).
The “mechanism” isn’t (I don’t believe) comprehensively understood, but includes alpha synuclein mis-folding and excess, mitochondrial stress, inflammation, excess iron, and calcium channel vulnerability.
I’m not rejecting the drugs. They probably target only one or two of the mechanism sinners. But they are not here yet. The most interesting may not be here for 10 years. I need something now. Non-drug options were therefore researched. Some common themes were obvious – manage stress, exercise vigourously, and the ketogenic diet and gluten avoidance.
It very rapidly became very obvious that microbiome and Parkinsons research is the new kid in town – with exponential interest from about 2015. The gut-brain axis generally has been on a rising trend for at least 20 years.
First – we get the idea that not only is there a problem with the bacteria in PWP – but it is sufficiently typical to be considered a potential biomarker
And again - sciencedirect.com/science/a...
Then – if you give mice poo from PWP they get PD (I paraphrase a lot)
So maybe , if you can change the bacteria in PWP, then you can significantly and usefully change the disease progress / mechanism
And maybe , whilst we wait for Parkinsons research to take an interest and start sponsoring research into specific targeted probiotics, it is possible to affect the microbiome with generic probiotics, prebiotics, natural fermented foods and other diet considerations
Or failing that – if faecal transplants work for mice…
This isn’t loony fringe stuff – its just that the need is more urgent for me than it is for mainstream science. But they’re looking at it
Already too long – but that’s why I’m Winnie the Poo!
*** - regarding Big Pharma, my parents met in the research labs of Boroughs Wellcome (now the Wellcome Foundation, part of Smithkline Beecham). My Dad then moved to Merck Sharpe & Dohme (MSD) where he spent the rest of his career. I remember him launching Sinemet and watching films on a projector of PWP recovering control. Dad was diagnosed with PD 4 years ago. My sister has spent a career at Pfizer.
Oh - and I was once involved with Interprise, a probiotic company who made species specific probiotics for calves and lambs as a treatment for scour, to keep antibiotics out of the food chain. There - disclosures done with