This is really interesting.
https://www.pnas.org/doi/10.1073/pnas.1705420114
and this is the company that they’ve spun out of the research:
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As is common in the startup world, it seems its had some challenges / pivots / mergers, etc … but seems to have good funding now:
Exclusive: ARCH-backed exercise-in-a-pill startup quietly laid off half its staff, ‘fully pivoted’ in October
In December 2019, a tiny decade-old California startup known as Cardero Therapeutics announced a new name — Epirium Bio — a new direction and $85 million in cash from blue-chip VCs such as ARCH and Vertex Ventures.
The company’s investigational pill has been tested in 110 patients total during Epirium’s proof of concept trials. But it hasn’t yet entered full-scale human trials, which are slated to begin early this year.
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It sounds as if it’s gone through a few iterations. I’m guessing this is fairly typical of early stage biotech. I noticed recently that it looks as though AgeX might be potentially be bought out in a reverse merger. I don’t know enough about the biotech space to speculate, but I assume it’s hard to cashflow early stage development long enough to raise the kind of money you need for trials.
Epirium sounds promising for sure. I hope that they can get it into clinical trails soon.
Hmmmm… The only clinical trial I can find for Epirium is this one:
https://clinicaltrials.gov/study/NCT04386304
Study Overview
Brief Summary:
This is a Phase 1, open-label, dose escalation study aimed at evaluating the safety, early efficacy and potential biomarkers of (+)-epicatechin in patients with Becker or Becker-like Muscular Dystrophy (BMD).
Detailed Description:
The safety and tolerability of three escalating doses of (+)-epicatechin will be assessed and early effectiveness measured by changes in plasma biomarkers, tissue biomarkers from muscle biopsies, cardiac imaging, and on clinical function assessments of participants’ muscle strength. All patients will receive oral (+)-epicatechin for a total duration of approximately 52 weeks. Three doses of (+)-epicatechin will be tested in sequential 2 month periods with total daily doses of 75, 150, and 225 mg/day (+)-epicatechin. Doses will be escalated every 2 months, if tolerated, for the first 6 months of the study. Participants will then continue to receive the highest does they tolerated for an additional 6 months.
Show more
OFFICIAL TITLE
A Phase 1, Open-label, Dose Escalation Study to Evaluate the Safety and Preliminary Efficacy of Orally Administered (+)-Epicatechin in Patients With Becker or Becker-like Muscular Dystrophy With Continued Ambulation Past 16 Years of Age
I assume MF-NCE1 is the Quinoxaline. Hard to know how long it will take to get it into trials.
I just found this post in our “Gray Hair reversal” thread and it made me wonder if the Dinoprostone Gel (that is available inexpensively from India) might be something that would be useful in reversing gray hair… as a similar drug has done it. It seems worth a try. Easy and cheap.
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Tim
#8
I kind of like my silver hair. When I run I can imagine that I am the Silver Flash.
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Yeah, really interesting. Might be worth a try.
I did a little digging and it looks as though Dinoprostone and Latanoprost work on different receptors. There are some other pharmaceuticals that affect PDFA2 like latanoprost. I haven’t heard of these drugs and I’m not sure how available they are: Sulprostone, Dinoprost Tromethamine and Carboprost Tromethamine all seem similar to Dinoprostone. FYI, I used Chat GPT to research this so it might not be accurate.
Seems reasonably accurate:
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jakexb
#12
I’m pretty sure PGE2 is increased by castor oil (I remember this from hair growth forums a few years back, castor oil was a big craze)
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If this 15-PDGH inhibition can restore/improve the motor end plate, the nerve/muscle junction, that would be a gigantic step. You can always gain muscle mass, even in old age. But there’s nothing you can do anything against denervation. if the muscle can’t receive any order from your brain because the junction becomes deficient, you’re dead, no matter the intensity of training.
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Interesting that bile acid inhibits 15-PGDH
Bile acids inhibit NAD±dependent 15-hydroxyprostaglandin dehydrogenase transcription in colonocytes
And then closing a possible loop is that either glycine or taurine (both increase longevity) are needed to produce bile acids:
Prior to their secretion into bile, bile acids are conjugated with the amino acids taurine or glycine (Hofmann et al. 2010). Conjugation substantially reduces the passive reabsorption of the molecule through biological membranes.
Bile Acids and longevity?
Intestinal microbes in people aged 100 or over produce unique bile acids that might help keep infections at bay . Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation.
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“Blau and her colleagues plan to investigate at a molecular level how neural growth is stimulated by blocking 15-PGDH activity. Blau has also co-founded a company, Epirium Bio, to develop similar drugs for use in humans. Although her lab is still conducting animal studies, the company hopes to launch a clinical trial within the next year or so.”
“Inhibition of 15-PGDH, a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. 15-PGDH acts in vivo as a negative regulator of prostaglandin levels and activity, provides a candidate target.”
Of course, she must think it is a good idea to block 15-PGDH, especially in old people trying to stave off sarcopenia.
But on the other hand, it might increase their risk of cancer.
15-PGDH
“15-PGDH (15-Hydroxyprostaglandin dehydrogenase) is a tumor suppressor in breast, colon, liver, lung, and pancreas since decreased expression of this enzyme is associated with increased tumorigenesis. 15-PGDH metabolizes intracellular PGE2 so that this ligand is unable to bind EP receptors, which results in suppression of PGE2 signaling”.
The tumor suppressor 15-PGDH is the key enzyme in prostaglandin E2 catabolism and is down-regulated in colorectal cancer (CRC) tissue. Canonical Wnt signaling is frequently elevated in colon cancers and has been shown to down-regulate 15-PGDH expression.
The most readily available 15-PGDH inhibitor that I could find is licorice root extract which contains β-Glycyrrhetinic acid.
I don’t think I will be adding any 15-PGDH inhibitors to my supplement list at this time.
https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2567.1997.00131.x
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Here is a link to the Empium Bio website. There are no updates in the past 3 years in their “news” section of the website, so I think that company may be dead now.
Jay
#18
DesertShores, You mentioned licorice root. Here is a PubMed study using Licorice Flavonoid Oil (LFO) to help increase muscle mass after rehabilitation treatment for osteoarthritis of the knee. I don’t see it readily available as a supplement, but I did find references in other articles to Licorice Flavonoid Oil (LFO: Kaneka Glavonoid Rich Oil ). Of course, licorice root extract is readily available, but I wonder how different it would be than the LFO? I will investigate this further.
The effects of licorice flavonoid oil with respect to increasing muscle mass: a randomized, double-blind, placebo-controlled trial - PubMed.
jakexb
#19
Fwiw castor oil is a very common substsnce that increases pge2
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Here is a bit more news on this topic.
Known drug restarts flow of brain cleaning fluids
The team then set out to see if they could revive the lymphangions and identified a drug called prostaglandin F2α, a hormone-like compound commonly used medically to induce labor and known to aid smooth muscle contraction.
The lymphangions are lined with smooth muscle cells, and when the researchers applied the drug to the cervical lymph vessels in older mice, the frequency of contractions and the flow of dirty CSF from the brain both increased, returning to a level of efficiency found in younger mice.
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