Catalyst Awardee

Project Description

Transformative oral drugs that reverse muscle weakness and aging in older adults

Stan Watowich, PhD; Harshini Neelakantan, PhD

Competition Sponsor: US National Academy of Medicine

Every adult over 40 years old faces the relentless loss of skeletal muscle strength, caused primarily by the inability of aging muscles to regenerate fully. In the elderly, decreased muscle strength leads to reduced mobility and physical activity, which places older adults at high risk for falls, fractures, chronic diseases, assisted living, and cognitive disorders. Muscle stem cells (muSC) are responsible for the muscle regeneration and repair that maintains muscle strength and function. Unfortunately, muSC become increasingly senescent during aging and cannot sufficiently regenerate and repair skeletal muscle to maintain strength. Current recommendations to reduce age-linked muscle weakness include resistance exercise and protein-rich diets; at best, these approaches provide modest benefits. Given the critical unmet need to prevent muscle weakness during aging, we are developing transformative drugs that reactivate aged muSC and reverse muscle degeneration and aging in older adults. Our drugs utilize a novel mechanism-of-action to reactivate aged muSC. We discovered that the enzyme nicotinamide N-methyltransferase (NNMT) is upregulated in skeletal muscle during aging and disrupts muSC energetics and function. In paradigm-shifting preliminary studies with aged animals, we demonstrated that NNMT inhibitors could double muscle strength, size, and muSC regenerative capacity. Support from the Healthy Longevity Global Competition will help accelerate preclinical development of a safe, once-daily pill that restores full muscle strength and function in aging adults. Our innovative therapy will provide numerous health, wellness, and economic benefits to the world’s ever-increasing elderly population, including increased healthy, productive, independent living. No comparable drugs exist in this space.

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