"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.
HN posts about mouse studies always trigger a bunch of skepticism. I’m a layperson so it’s hard to separate the informed comments from me-too contrarians.
Are there areas of medicine where mouse models have a much higher or lower success rate in human trials?
There's two issues, success rate (about 5%) and time ... even if it is successful in humans, it will be 5 to 10 years before it's available (and 20-30 before it's affordable)
To be fair, this same realist perspective seems to suggest humans would not have been capable of developing a COVID vaccine for 5 to 10 years; yet, they identified the virus and authorized vaccine use within eight months.
Not to diminish the accomplishment of rolling out the Covid vaccine in such a rapid timeframe, but… there was something like 40+ years of research into creating mRNA vaccines that laid the ground work.
I’ve had my shoulders “cleaned up” arthroscopically, and the pain is still a major preventer of movement. I would love to stay on the mats longer with something that doesn’t harken to medieval times. So excited at this prospect.
It does get better with physio and exercise. Took me twenty years to recover full (100%) pain-free mobility. It still occasionally finds itself in an uncomfortable spot that can be self-freed, but it can now hold muscle tone across the fascia.
Well, the article notes that it seemed effective on human tissue samples.
The researchers also tested cartilage taken from patients undergoing total knee replacement for osteoarthritis. After one week of treatment with the 15-PGDH inhibitor, the tissue showed fewer 15-PGDH-producing chondrocytes, reduced expression of cartilage degradation and fibrocartilage genes, and early signs of articular cartilage regeneration.
So, IMO that shows hope for once it goes to trials.
Would this work for rheumatoid arthritis? I don’t know anything about it myself so it could be a completely different thing, but someone I know has it and it is awful. Would be great to see a treatment coming through.
A study led by Stanford Medicine researchers has found that an injection blocking a protein linked to aging can reverse the natural loss of knee cartilage in older mice.
If only a small percentage of studies make it past the mice stage to be tested on humans, it means that a lot more studies have been done on mice than humans. Hence, we know more about mouse biology than human biology. So over time, it must get easier and easier to generate positive results in mice, which are uncorrelated with the success in humans.
It's worse than that. People get to interfere in mice. You can stunt their growth, give them transparent skin, grow more or less limbs, cut into them ... you can't experiment at all on humans.
Especially when it comes to pregnancies we know more about a lot of animals than about humans. Why? Well pregnancies is how you multiply meat in animals, which is what farmers are interested in (and pay for). Which ironically also means animal pregnancies can be treated in case of trouble much more effectively.
Why pregnancies? Pregnancy changes a LOT of chemical processes in the body and so quite a bit of "normal" medical knowledge doesn't apply to pregnant women. Which has caused the medical establishment to declare anything that isn't explicitly tested on pregnant women as a no-go zone. So even problems and medications that we do know about, doctors won't apply them to pregnant women.
Yes there are metabolic changes in the mother herself during pregnancy but that's not why it's hard to research. The main fear is that drugs will cross the placenta and affect the growing fetus, or similarly be transmitted through breast milk to an infant. Very young humans are uniquely vulnerable to disruption in their growth that can cause life-long problems.
I’m familiar with Helen Blau, her team is into everything: telomeres and aging, reversing cardiomyopathy, HIV, that team is really hardcore into prolonging and improving lives and wellness.
Heard.
But if even one of their interests panned out it would be paradigm changing for millions and they’re doing it to save your lives not get a updoot on hacker news. They’re all pretty anonymous and understated Imo but i am a great fan and i would love for it to be the “year of” anything they’re studying. I listed a few and I’m sure there’s dozens I’m unaware of.
I’ve been thinking that this stuff is all more closely related than we think and that as they go down one of these paths they’re finding all this other stuff along the way, it’s genuinely fascinating.
Heart disease and failure is one of the biggest ways we meet our ends right now. There’s so much interplay between aging processes, ceasing t-cell production, shortening telomeres , that ties in together with this and im glad they see a bigger picture than me having another 20 years , too winded to stand up and piss or strapped to a bed hooked to tubes and groaning!
I feel it's unfair to ding Linux on this, even with the implied "slightly less".
I've had Windows as my main personal computer for practically forever, because of games. Before that it was DOS. That changed a couple months ago.
Literally just now--in preparation for this comment--I decided to try something I never tried before: I mounted my Win10 drive, picked an arbitrary old Windows game EXE (2006 "Prey" game demo), and launched it as a "non-Steam game" with just one little drop-down menu tweak... and it launched to the main menu!
In the the "years of the Linux desktop" of my youth, that capability was unthinkable, or would quickly foul with terrible performance. Now it means the only reason for me keep my old drive for dual-boot involves games that go out of their way to interfere with clumsy anti-cheat rootkits.
basically every growth process in the body can be induced by chemicals. and so now people are starting to take some of these chemicals. we will see how it turns out
My dream is to be able to run again. Please. Let me run a 10k at least once more in my life. To feel that stillness and freedom and calm that sets in when the brain start going to hibernation after about 7km.
Hope you see your dream realized. But know that that stillness is achievable through other activities as well. Most directly and deeply, through a meditation practice which is geared towards reaching those deep meditation states (called Jhanas in the Pali canon). My favorite guide on that particular path is Leigh Brasington.
>Human cartilage samples taken from knee replacement surgeries also responded positively. These samples included both the supportive extracellular matrix of the joint and cartilage-producing chondrocyte cells. When treated, the tissue began forming new, functional cartilage.
Once again, not in humans, in mice. We don't know if the same result happens in humans. At all. We need to proceed to clinical trials to determine if a result is indeed positive.
I had good results with hyaluronic acid for knee osteoarthritis. Sometimes they sell it as Type II Collagen. "Source Naturals Hyaluronic Joint Complex" was the best for my relatives/friends' knee problems. I take it a few times a month (with resveratrol) for smooth skin. I have been taking it since 2008 without any negative result.
Seems like it should work. I do not have experience with that condition. A quick search online (patella tendonitis hyaluronic acid) yielded this study: https://pubmed.ncbi.nlm.nih.gov/22526713/
So they are using hyaluronic acid injections for patella tendonitis. Taking hyaluronic acid orally would probably take longer for effects compared to injections. Most people would prefer the injections because they feel safer for a doctor to do all the work. I prefer the tablets. If you have the money, I guess go for the injections. I would use the H.A. tablets. (With a tall glass of water, and do not take at the same time as blood-thinning medication, like pain killers or drugs.)
You should check out Michael Levin. Cancerous cells do not grow organ-like structures. Normal cells communicate with other cells as a network to control growth.
A small molecule inhibitor of 15-hydroxy prostaglandin dehydrogenase causes cartilage regeneration. I hope they fast-track it to human trials.
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