5 ms·

https://www.science.org/doi/10.1126/science.adx6649 https://www.science.org/doi/10.1126/science.adx6649 A small molecule inhibitor of 15-hydroxy prostaglandin

by tima101 8mo ago

https://www.science.org/doi/10.1126/science.adx6649 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.

fraserharris 8mo ago
"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
- mobilejdral 8mo ago
  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.
  - shermantanktop 8mo ago
    EDS and arthritis go together so I wonder if we could see secondary effects on other EDS symptoms like subluxation or GI issues?
  - amluto 8mo ago
    > Anyone can do this today Please explain
    - RealityVoid 8mo ago
      Yes, I deff want this explained, since I'm missing about half of my meniscus.
    - mobilejdral 8mo ago
      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.
      - esperent 8mo ago
        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?
        oarfish 8mo ago
        never heard of that, sounds wild. Any source for this?
    - betty_staples 8mo ago
      [flagged]
robocat 8mo ago
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
JumpCrisscross 8mo ago
It looks like this enzyme uses NAD+ as a substrate?
ricksunny 8mo ago
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.
- stanford_labrat 8mo ago
  the small molecule is SW033291, papers are required to publish this specific detail but second order news sources tend to avoid the technical details.
  - ricksunny 8mo ago
    Thank you. Benefiting from which, for others, here is the structure. https://pubchem.ncbi.nlm.nih.gov/compound/3337839#section=2D-Structure https://pubchem.ncbi.nlm.nih.gov/compound/3337839#section=2D...

by tima101 8mo ago

fraserharris 8mo ago

"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

mobilejdral 8mo ago
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.
- shermantanktop 8mo ago
  EDS and arthritis go together so I wonder if we could see secondary effects on other EDS symptoms like subluxation or GI issues?
- amluto 8mo ago
  > Anyone can do this today Please explain
  - RealityVoid 8mo ago
    Yes, I deff want this explained, since I'm missing about half of my meniscus.
  - mobilejdral 8mo ago
    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.
    - esperent 8mo ago
      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?
      - oarfish 8mo ago
        never heard of that, sounds wild. Any source for this?
  - betty_staples 8mo ago
    [flagged]

robocat 8mo ago

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

JumpCrisscross 8mo ago

It looks like this enzyme uses NAD+ as a substrate?

ricksunny 8mo ago

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.

stanford_labrat 8mo ago
the small molecule is SW033291, papers are required to publish this specific detail but second order news sources tend to avoid the technical details.
- ricksunny 8mo ago
  Thank you. Benefiting from which, for others, here is the structure. https://pubchem.ncbi.nlm.nih.gov/compound/3337839#section=2D-Structure https://pubchem.ncbi.nlm.nih.gov/compound/3337839#section=2D...