Hir again something interesting .... Does anyone have more information?

[PDTom]

gazette.com/news/local/colo...

[JayPwP]

What is your opinion?

[jeffmayer in reply to JayPwP]

I hope it's not another false dawn

[kevowpd]

Youd think, well i would anyway, that the University of Colorado would be able to run a ph2 trial without spending 10m in extra money.

Some more info about the drug:

en.m.wikipedia.org/wiki/Gly...

Also known as 'phenylbutyrate-triglyceride'

[WinnieThePoo in reply to kevowpd]

$10 million is about right for a phase 2 PD disease modification trial cost. And then if that works reckon on another 20 million for the phase 3

[Zardoz in reply to WinnieThePoo]

Isn't some form of butyrate the result of mannitol's breakdown, sent along the vagus nerve to the brain?

[Bolt_Upright]

That story seems to cover everything pretty well.

[JAS9]

When I first saw your post I was very skeptical. But once I read about it, I'm not so sure. I can see MJF'F's point; it must be hard to evaluate all of the claims. But they take in $millions a year, and it is what they claim they do. Too bad it's not as easy to get as B1 or many of us would be using it by now. Seriously though this system is broken and needs to be fixed. But then, don't we all.

[chartist]

PDTom,

High dose melatonin (HDM), which is also an HDAC inhibitor, has shown similar benefit in PD animal models at human equivalent doses of around 120 ~ 320 mg/day.

researchgate.net/figure/Eff...

Melatonin has already shown benefit in PwP at 10 and 50 mg/day. A 200~320 mg/day PwP study is needed and probably significantly less expensive than a Phenyl butyrate study and likely significantly faster in years to complete, but apparently MJFF is not interested in funding either. Melatonin has an excellent safety profile in comparison to any drugs commonly used for PD treatment.

I'm not knocking the article you posted, just trying to be realistic about the possibility of such a study ever taking place since 8 years have already passed since his animal model study.

Art

[SilentEchoes]

Phenylbutyrate is already being trialed for ALS. Big uproar in this community because the FDA wasn't going to approve Amylyx (not a big enough money maker). It's a combination therapy of sodium phenylbutyrate and ursodoxicoltaurine (Phenylbutyrate and Tauroursodeoxycholic acid (TUDCA)). It works on the uric acid cycle to detox ammonia excess.

Amlyx/ALBRIOZA™ (also known as AMX0035) has been approved in Canada for ALS.

I'm tired of big pharma's games. TUDCA is an over the counter supplement and you can get sodium phenylbutyrate online from CanChema or just take butyrate + TUDCA.

Too tired to do a write-up, easy enough to fact check me.

SE

[Boscoejean in reply to SilentEchoes]

so you are saying that you think that taking butyrate plus TUDCA could have a similar result?

[SilentEchoes in reply to Boscoejean]

Yes. I believe alpha-synuclein is a down stream effect not a causitive factor - we need to be looking at TDP-43.

medicalxpress.com/news/2022...

[Boscoejean]

clinicaltrials.gov/ct2/show...

[kevowpd in reply to Boscoejean]

They dont seem to have published the results of that study.

[Boscoejean in reply to kevowpd]

I noticed that and wondered why

[kevowpd in reply to Boscoejean]

Blood will be drawn on two days prior to starting phenylbutyrate to measure alpha-synuclein concentrations. Phenylbutyrate-triglyceride will then be started and the change in plasma alpha-synuclein will be measured on day 1, 7, 14, and 21 days while taking phenylbutyrate. After 21 days, the drug will be stopped and a final blood sample will be measured at 28 days to see if plasma alpha-synuclein has fallen to its pre-phenylbutyrate level.

Im confused. Presumably the hypothesis is that the drug reduces asyn in plasma? Should it say 'risen' where it says 'fallen'?

Edit: nevermind. The hypothesis is that higher plasma asyn is better since it (hopefully) reflects removal from the brain.

[MBAnderson in reply to kevowpd]

Wonder why??

[kevowpd in reply to MBAnderson]

Im in no way across all of the possible reasons but the first that comes to mind is that, as youve said, it didnt go that well.

[Boscoejean]

ravictihcp.com/about-ravict... for UCD

Urea cycle disorders (UCD) are a group of genetic diseases that prevent the body from safely detoxifying ammonia. Ammonia is produced by natural turnover of proteins and nucleic acids in our bodies, as well as by the breakdown of dietary proteins.

Urea Cycle Disorders (UCD) - Center for Genetic Medicine ...

[SilentEchoes]

Thanks for clarifying my comment (uric acid/Urea cycle) to detoxify ammonia. I was tired! Ammonia levels are reported to be elevated in pALS, there a several metabolic pathways for our bodies to produce ammonia that are not genetic. pubmed.ncbi.nlm.nih.gov/257...

[Kia17]

Falling from the frying pan into the fire

Ammonaps (sodium phenylbutyrate) is a medication used for the treatment of patients who have urea cycle disorders.

Neurologists sometimes prescribe Ammonaps for off-label treatment of people suffering from ALS.

Side effects;

Common or very common

Abdominal pain; anaemia; appetite decreased; constipation; depression; headache; irritability; leucocytosis; leucopenia; menstrual cycle irregularities; metabolic acidosis; metabolic alkalosis; nausea; oedema; renal tubular acidosis; skin reactions; syncope; taste altered; thrombocytopenia; thrombocytosis; vomiting; weight increased.

[MBAnderson]

The reason he can't get funding is it doesn't work.

Another Don Quixote.

PS. If the guy in the red shirt wearing the crocks is a professor of neurosurgery, I wouldn't let him operate on me.