This popular science article is a reminder that all too little in this world happens for entirely rational reasons. Drugs aimed at slowing or reversing the age-related loss of muscle mass leading to sarcopenia are presently under development by a number of companies, though none of the candidates discussed are producing effect sizes that look very favorable in comparison to the effects of resistance exercise. These efforts will likely benefit from the present manufactured hype that attends the use of antidiabetic GLP1 receptor agonists for weight loss, as one of the side-effects of this drug is modest loss of muscle mass. To the extent that this aids in the development of meaningful ways to treat sarcopenia, fair enough. But one is left with the lingering feeling that perhaps this is not the best way to make progress. Will these companies continue to work on age-related disease, or will they just get shunted into the non-aging-related hype of the day? The latter is not a small risk.
Even as obesity treatments Ozempic and Mounjaro continue their surge in popularity, drug hunters are asking whether it is possible for people to lose weight on these glucagon-like peptide-1 (GLP-1) agonists without losing muscle. Drug candidates originally designed to build, preserve or regenerate skeletal muscle for treating muscle atrophy in degenerative conditions or ageing are now being tested in combination with GLP-1 agonists used for obesity to spare lean muscle.
One such biotech is BioAge Labs. In February, the company announced a $170-million series D financing, which will allow it to combine its apelin receptor agonist azelaprag (BGE-105) with Eli Lilly's GLP-1 agonist Mounjaro (tirzepatide) in phase 2 studies. The combination preserved lean body tissue in phase 1 studies and animal models and boosted weight loss by 10-15% compared with Mounjaro alone. The news came on the heels of Regeneron's intention to launch a phase 2 trial pairing the company's muscle-preservation monoclonal antibodies (the anti-myostatin trevogrumab and the anti-activin A garetosmab) alongside Novo Nordisk's Ozempic (semaglutide).
Immunis and Juvena Therapeutics are zooming in on the muscle stem cell secretome - the collection of proteins, including growth factors, cytokines, chemokines, and extracellular matrix components, secreted by muscle cells. The secretome kicks in to boost proliferation in response to exercise or to enhance cellular interactions to accelerate wound healing, for example, and it declines markedly with age. For Paris-based Biophytis, the focus is on the shared pathways between age-related sarcopenia and neuromuscular disease such as Duchenne muscular dystrophy. Its lead candidate is ruvembri (BIO101), a small molecule that targets the MAS receptor, which is present in cardiorespiratory and skeletal muscles. MAS activates the AKT and AMPK kinase pathways downstream, stimulating protein synthesis and energy production, respectively.
Companies with muscle-building drugs are now blazing a trail in obesity studies to counter the skeletal muscle atrophy that accompanies fat-loss treatments. The often dramatic weight loss experienced by people who have undergone bariatric surgery or are taking GLP-1 agonists such as Mounjaro and Ozempic leads to the loss of muscle as well as fat. As a consequence, biopharma companies are on the lookout for drugs to use alongside GLP-1 agonists to preserve lean muscle mass.
Link: https://doi.org/10.1...587-024-02176-5
View the full article at FightAging
