A Pill to stop Parkinson's
 

Interesting ... trials to begin in 2019

World-first pill may stop Parkinson's | The New Daily

This looks very promising.

The journal in which the work was published (Science Translational Medicine) is outstanding.

It has an impact factor of 17 which means that the average paper in it is cited by 17 other papers every year; only top-quality work gets published in it.

Disappointing 1: the underlying paper is behind a paywall.

Disappointing 2: according to the New Daily article,
"The biggest hurdle, apart from funding, is that MCC950 came off a patent. This means the researchers have had to develop variations of the original drug for intellectual property reasons. Those new drugs are currently being tested and, according to Dr Woodruff, proving to be even more effective."

But, the good news is that there are plenty of natural compounds in this area. See [2].

Has anyone tried low dose aspirin?

References:

[1] "Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice"
Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice | Science Translational Medicine

[2] "Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production
József Tőzsér1 and Szilvia Benkő2
Mediators of Inflamation, Aug 2016
https://www.hindawi.com/journals/mi/2016/5460302/

John

There is some evidence from mouse models that low dose aspirin can increase dopamine levels in the brain through activation of tyrosine hydroxylase.

Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson's Disease. - PubMed - NCBI

Unfortunately, the "aspirin" paper is behind a paywall. But based on the abstract ...

I don't get why a PwP would benefit more from increased tyrosine hydroxylase levels than from just increasing their levodopa dose.

Tyrosine hydroxylase (TH) is the rate-limiting factor in the conversion of tyrosine to levodopa. But, as I understand it, it is not directly involved in the conversion of levodopa into dopamine. [1, infered from figure]

......................TH.......................... .........AADC
tyrosine --------------------> levodopa ------------------> dopamine

So, as I understand it, increasing TH leads to an increase in endogenous levodopa.

But couldn't this benefit be more easily met by increasing the intake of exogenous levodopa?

Perhaps the marginal benefit of increasing TH over increasing exogenous levodopa comes from TH having a longer half-life. Perhaps, it also has better localization properties.

Reference:

[1] Tyrosine hydroxylase - Wikipedia

John

It is annoying that the paper is behind a paywall.

What seems to be going on is that it is known that the tyrosine hydroxylase gene contains a CRE element. The CRE element binds a protein called CREB; this is what they showed is enhanced by aspirin. CREB is a transcription factor; it activates the tyrosine hydroxylase gene, leading to production of more tyrosine hydroxylase protein in the nigra and hence more L-DOPA there as in your scheme.

Whether this works in people as well as mice remains to be seen. Also, I don't know enough about the pharmacology of exogenous/therapeutic L-DOPA to know to what extent its transport into the brain is rate-limiting.

I wish I had known about this before. An uncle of mine (in NZ) died from PD. I would have suggested low-dose aspirin to him.

I don't have the research paper ... but I have the next best thing. An SoPD blog post about the research paper!

Aspirin: Barking up the right tree? | The Science of Parkinson's

And just when you thought it was safe to get back in the water ...

Yet another article about MCC950!!!

But relax. It's OK. This one is an SoPD blog post from Simon :-)

Brain. On. Fire. | The Science of Parkinson's