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by tima101 147 days ago
https://www.science.org/doi/10.1126/science.adx6649

A small molecule inhibitor of 15-hydroxy prostaglandin dehydrogenase causes cartilage regeneration. I hope they fast-track it to human trials.

4 comments

"Phase 1 clinical trials of a 15-PGDH inhibitor for muscle weakness have shown that it is safe and active in healthy volunteers. Our hope is that a similar trial will be launched soon to test its effect in cartilage regeneration" - Helen Blau, Baxter Laboratory for Stem Cell Biology & the Donald E. and Delia B. Baxter Foundation Professorship
ERa activation promotes PGE2 resulting in decreased 15-PGDH.

So this is one of those standard poor estrogen signaling downstream things and simply improving the estrogen signaling and you get improved cartilage. Anyone can do this today along with getting all of the other positive effects. Those with EDS who have say variants on their TNXA/B have poor production ability to start and so we do everything we can to improve their cartilage production as they can only make so much which include doing stuff like this.

> Anyone can do this today

Please explain

It depends on the person and their genetics. The further you get from the ERa the more complicated this gets and simply stating "Do X" wouldn't apply to everyone even if there are some incredibly common things to do. I might know all the upstream genes, their interactions, and symptoms by heart so it is pretty easy to identify, but general advice would go something like: eat well, get sleep and exercise.
I've read that specific type of exercise (repeating cycles of low impact move, cycling, rowing, elliptical machine) are the most effective at triggering cartilage growth. Is that accurate?
never heard of that, sounds wild. Any source for this?
Yes, I deff want this explained, since I'm missing about half of my meniscus.
EDS and arthritis go together so I wonder if we could see secondary effects on other EDS symptoms like subluxation or GI issues?
They already have a human trial in progress...

It is being trialed to prevent muscle weakness and some of those patients will have arthritis and they can be assessed for statistical improvement.

Same thing happened with GLP1

It looks like this enzyme uses NAD+ as a substrate?
Because paywall I'm unable to open the paper, but do they ever specify the structure of the small molecule itself? In the associated non-paper materials (news pieces etc.) isn't identified beyond the name they gave it, PGDHi.

Getting vibes like a compsci paper that describes all about what an algo does but hides the sourcecode itself.

the small molecule is SW033291, papers are required to publish this specific detail but second order news sources tend to avoid the technical details.
Thank you. Benefiting from which, for others, here is the structure. https://pubchem.ncbi.nlm.nih.gov/compound/3337839#section=2D...