Promising results for a GLP-1 receptor agonist. Exenatide group of PwP showed improved motor function in a randomised, double-blind trial.

[ElliotGreen]

I first read about GLP-1 receptor agonists recently. They are diabetes drugs.

However, I immediately thought that they would be a great thing to try for Parkinson's.

Why? Because GLP 1 receptor agonists can lower inflammation, calm microglial cells, and reduce programmed cell death.

Well, it turned out that the Cure Parkinson's organization already has been investigating this class of drugs for benefits to people with Parkinson's.

So far, there are three existing drugs in the GLP-1R agonist class. They are called liraglutide, lixisenatide, and exenatide. This study is about exenatide. All three of these drugs are delivered by injection. (Bydureon is just a form of exenatide that you only have to take once a week, instead of daily.)

CURE PARKINSON'S WEBPAGE ON THE STUDY:

cureparkinsons.org.uk/news/...

quote:

“This is a very promising finding, as the drug holds potential to affect the course of the disease itself, and not merely the symptoms. With existing treatments, we can relieve most of the symptoms for some years, but the disease continues to worsen.”

-- Professor Tom Foltynie (UCL Institute of Neurology).

LANCET ARTICLE :

Athauda, Dilan, et al. "Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial." The Lancet 390.10103 (2017): 1664-1675.

thelancet.com/journals/lanc...

This is a 2017 article. There are other studies underway. Another GLP-1R agonist, Lixisenatide, may be more effective. There are various things to consider.

[WinnieThePoo]

It's been around a while. I participated in a webinar with the trial organisers. Phase 2 finished nearly 2 years ago now and phase 2 trials are under way on other glp1 receptor agonists but the phase 3 for exanatide hasn't even been announced.

[ElliotGreen in reply to WinnieThePoo]

I know this is from a couple of years ago, but it's new to me.

Do you know if anyone maintains a list of promising Parkinson's disease therapies?

So far I've been finding out about things in an organic and somewhat scattered fashion!

[WinnieThePoo in reply to ElliotGreen]

The science of Parkinsons is as good a central source as any I can think of

The preview of the year scienceofparkinsons.com/201...

covers a lot of areas of interest

[jeffreyn in reply to ElliotGreen]

There is a useful spreadsheet at the PD Trial Tracker website:

pdtrialtracker.info/

Click on the link called "collaboration" (near the top right corner of the webpage), and then click on the link called "Disease-Modifying Therapies in the PD Trial Pipeline (date of last update)".

[jeffreyn]

Simon did a substantial SoPD blog post on GLP-1 receptor agonists (Exenatide in particular) about a year ago.

scienceofparkinsons.com/201...

[ElliotGreen in reply to jeffreyn]

Simon at SoPD has actually written FIVE posts about Exenatide:

1. Initial discussion of phase 2 clinical trial results. (2017)

scienceofparkinsons.com/201...

2. A follow-up editorial. (2017)

scienceofparkinsons.com/201...

3. The substantial post you linked to above. (2018)

scienceofparkinsons.com/201...

4. Who responds best to exenatide? Simon reports on a follow-up publication. (2018)

scienceofparkinsons.com/201...

5. Exciting Exenatide Exosomes, about another follow-up publication. (2019)

scienceofparkinsons.com/201...

Here are the two follow-up scientific publications that Simon addressed in the last two articles:

1. Athauda, Dilan, et al. 2019. Post hoc analysis of the Exenatide‐PD trial—Factors that predict response. European Journal of Neuroscience, 49(3), pp.410-421.

onlinelibrary.wiley.com/doi...

"In the subgroup analyses, exenatide once-weekly was associated with broadly improved outcome measures assessing motor severity, non-motor symptoms, cognition and quality of life across all subgroups, however tremor-dominant phenotype and lower MDS-UPDRS Part-2 scores predicted greatest motor response to exenatide and there was an indication that patients with older age of onset and disease duration over 10 years responded less well."

2. Athauda, Dilan, et al. 2019. Utility of neuronal-derived exosomes to examine molecular mechanisms that affect motor function in patients with Parkinson disease: a secondary analysis of the Exenatide-PD trial. JAMA neurology, 76(4), pp.420-429.

ncbi.nlm.nih.gov/pubmed/306...

Here, they used exosomes from the brain, which circulate in the blood, to examine the effects of the drug in the brain. Very exciting, because it normally hasn't been easy to track the effects of drugs in the brain.

[ElliotGreen in reply to jeffreyn]

Also, he notes that "some of the investigators involved in the study have ... published an OPEN ACCESS commentary in the Journal of Parkinson’s disease." This was back in 2017, following the publication of the initial results of the phase 2 trial.

content.iospress.com/articl...