Suppression of Inflammatory Signaling as a Treatment for Frailty
Age-related frailty is accompanied by marked chronic inflammation, and indeed much of the physical weakness of frailty is likely caused by long-term inflammation and the ways in which it disrupts muscle tissue maintenance. The tools presently available to suppress inflammation are somewhat blunt, interfering in the necessary signaling needed to maintain a normal immune response, as well as in the unwanted overactivation of the immune system found in older people. Nonetheless, such tools are slowly becoming better and more selective over time, and some are now being tested as treatments for frailty.
Earlier this year, MyMD Pharmaceuticals merged with Akers Biosciences to form a new company focused on developing and commercialising novel immunotherapy therapies. The company's lead compound is MYMD-1, an indirect inhibitor of TNF alpha. The company CSO refers to the trial in January as a "sarcopenia/longevity" study, because "the FDA isn't accepting longevity or aging as an indication." There's also the fact that a true longevity study would require following people for many years, so it makes sense to focus on "markers like muscle loss, weakness, frailty, increased predisposition for age-related pathology, and the like."
The key proposition behind MyMD-1 is its ability to reduce chronic inflammation through the inhibition of several key cytokines, including the oft-cited TNF alpha. "TNF alpha is the star of the show. It's the first proinflammatory cytokine to go up when you get an infection or any type of inflammatory illness, and it turns on IL-6 and IL-1. It is the innate immune response, but it also gets out of control in autoimmune diseases. MyMD-1 is also selective, meaning that it doesn't take out innate immunity, but it does affect adaptive immunity, so we have selectivity there and we think that's going to make a big difference."
A mouse study conducted over the past couple of years and now submitted for publication has produced what sounds like some pretty exciting results. The study looked at the effect on lifespan on older mice (19 months old) treated with either MyMD-1, rapamycin, or a combination of rapamycin and metformin over a period of 13 months. "They saw that MyMD-1 resulted in a much more dramatic, fourfold-increased, highly statistically significant survival time. In addition, they saw absolutely no loss of muscle strength in male mice compared to those on the other compounds. Females had some loss, but nothing like they did in the other groups. What we're all looking for is a chance to slow aging and extend healthspan, and we think that this is happening both because of the anti-inflammatory effects of MyMD-1 and because it also blocks oxidative stress and things like fibrosis. We think it's the combination that really does the heavy lifting."
Link: https://www.longevity.technology/mymd-to-commence-phase-2-trial-in-frailty/
...they saw absolutely no loss of muscle strength in male mice compared to those on the other compounds...Females had some loss, but nothing like they did in the other groups...
this is quite important if it translates to human. Forget about longevity, lifespan and such. Imagine how many people could get improved quality of life and avoiding disability .
In the article they hint that the compound might be helpful against multiple sclerosis. I don't know if directly or with some modifications. That one would be a biggie too.
Well, it is an " immunometabolic regulator", thus could be almost anything eg fisetin in high dose.
OTOH they evidently specialise in "plant alkaloids". Could be berberine - never yet investigated in high dose so far as I know .
We already know that Mymd-1 is Isomyosmine.
From the patent:
https://www.sciencedirect.com/science/article/abs/pii/S0165572819302206)
"Isomyosmine (3-(3,4-dihydro-2H-pyrrol-2-yl)-pyridine) is a nicotine related alkaloid present in solanecea plants containing nicotine…. it is believed that isomyosmine has a unique ability to affect basic cell function and directly and/or indirectly inhibit the production of Reactive Oxygen Species (ROS), particularly hydrogen peroxide (H2O2)…. Isomyosmine may be prepared synthetically using known techniques, and also is commercially available from several chemical suppliers"
This application discusses - As an alternative to synthetic preparation, isomyosmine may be obtained by extraction from tobacco or other materials in which it occurs naturally.
https://patents.justia.com/patent/10806728
I've heard Brian Kennedy in recent interviews talk about the effectiveness of AKG with inflammation and frailty.
Can't wait for the publication of their lifespan study in mice. 95% survival when all of the control mice (who were given rapamycin and metformin!) are dead. And only started treatment at 19 months (65 years in humans) See figure page 13 of their corporate presentation. https://d1io3yog0oux5.cloudfront.net/_cceb84ecfd24ef23cdc84451187998aa/mymd/db/2216/20661/pdf/MyMD-Investor_101321_FINAL.pdf