Exenatide supposedly stopped Parkinson's degeneration
 

Thanks Dan. This is the link for CPT's press release with a little more info:
Cure Parkinson's Trust | Breaking News: Diabetes Drug Shows Potential as Disease-Modifying Therapy for Parkinson’s

I received the the full publication last evening but haven't had a chance to review it yet (I will over the weekend). I would be happy to email to anyone who is interested.

Gary

My only quibble is the use of the word "stopped" (i.e. it's a bit too strong). In the title of the article they use the words "may" and "slow".

Also, in the abstract of the research paper they say [1]:

"Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain."

[1] Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial, Athauda et al., The Lancet, 03 August 2017.
http://www.thelancet.com/journals/la...585-4/fulltext

earlier discussion of exenatide (Byetta)
 

Drug was first ok'ed by the FDA in 2005.
https://www.neurotalk.org/parkinson-...n%27s+diabetes

A couple of good write-ups (IMHO) on the exenatide trial, from the SoPD blog and from Parkinson's UK.

Exenatide: One step closer to joblessness! | The Science of Parkinson's disease

Exenatide — latest trial results explained – Parkinson’s UK – Medium

In my opinion, although hoping for the best, we should be cautious about how we interpret these results.

The Cure Parkinson's Trust report says [1]:

"The participants did not report noticeable improvements in their symptoms during the trial period beyond what their standard medication already did for them."

Although progression is usually slow in PD, one would still have expected some comments along the lines of "I've had a good year". This raises the question of whether the MDS-UPDRS is the correct measure to use for assessing the efficacy of progression slowing drugs. In my opinion, there is too low a priority given to non-motor symptoms.

The "Science of Parkinson's disease" gives graphs of the results [2]. Even at face value, the size of the changes are small: after 48 weeks, the difference between the placebo group and the Exenatide group is only about 4 points on the MDS-UPDRS part III scale, motor examination [3]. Part III adds 33 scores each of 0, 1, 2, 3, 4, giving a total score of from 0 (good) to 132 (bad).

The Exenatide graph show a steep improvement from the baseline at time 0 to the next measure after 12 weeks of taking the drug, a fairly flat performance during weeks 12 to 48 where the drug is taken throughout, followed with a decline in performance once the drug is removed. This may indicate not a slowing of progression but, rather, a symptomatic effect.

Tupelo3, I'll be grateful if you could point me to the full paper.

References:

[1] Cure Parkinson's Trust | Breaking News: Diabetes Drug Shows Potential as Disease-Modifying Therapy for Parkinson’s

[2] Exenatide: One step closer to joblessness! | The Science of Parkinson's disease

[3] Rehab Measures - Movement Disorder Society sponsored Unified...

John

The reviews posted by everyone above are as good as you can find, so I don't think I need to add much more. I do agree that we need to be positive, but cautious, about these results, no different than any other small phase two study.

That being said, I'm not as concerned as others about the relatively small difference, which was statistically significant, between the groups. Exenatide is believed to slow PD progression more so than reverse it. One year is not that much time in the normal progression of PD symptoms. Just think about how each of us vary from day to day. I don't think any of us would notice a two point UPDRS improvement or decline. I think the mild improvement in the test group compared to the mild deterioration in the placebo group is about all you could have hoped for over the course of one year. I also think that difference, along with the important DatScan results, is "indicative" of the drug effect being neuroprotective rather than just symptomatic. I would imagine that the Phase 3 trial, which will happen sometime in the future, will be longer term. It will probably be in the range of three years, like the design of the current ongoing Isradipine trial. Unfortunately, that's the time that is needed to see meaningful differences in progression compared to a placebo.


Gary

More write-ups!
 

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

A couple more exenatide write-ups!

The SoPD blog has had another go at it, and the researchers have written an open-access editorial.

Exenatide: An editorial | The Science of Parkinson's disease

Is Exenatide a Treatment for Parkinson’s Disease? - IOS Press

What is the relationship between alpha-synuclein and Exenatide?

Given the supposed centrality of alpha-synuclein in the pathogenesis of PD, you would expect any treatment which slowed the progression of PD to involve alpha-synuclein in some way.

John

Exenatide update
 

Quite a bit has happened since we last discussed exenatide.

This recent post on the SoPD blog can help bring us all up to date. :-)

What do you do with a problem like Exenatide?:
What do you do with a problem like Exenatide? | The Science of Parkinson's