SARM1 Inhibitors
SARM1 inhibitors are an emerging and investigational class aimed at preventing programmed axon degeneration. In the neurodegeneration landscape, this is one of the most mechanistically exciting newer categories because it targets a relatively clean execution pathway rather than a broad downstream symptom.
Biological Rationale
SARM1 is the key driver of axon self-destruction. Once activated, it depletes NAD+ and pushes axons into energetic collapse and fragmentation. The rationale for SARM1 inhibitors is therefore direct: if axon degeneration is an active pathway, then blocking the executioner could preserve function across conditions such as CIPN, ALS, TBI, or stroke.
Evidence Strength
Emerging
This is not yet a proven therapy class for patients. What makes it notable is not mature clinical evidence, but the unusually strong mechanistic grounding and broad disease relevance. Lilly’s acquisition of Disarm Therapeutics, and advancement of LY3873862 to stage II clinical trial, specifically highlighted SARM1 inhibition as a disease-modifying strategy for axonal degeneration in disorders such as ALS.
Limitations
This category remains investigational and as of yet there are no drugs on the market. There is no established patient benefit yet, unclear breadth of efficacy across diseases, and the usual translational hurdles of target engagement, CNS penetration, safety, and trial design. It is exciting but not part yet of standard clinical care.
Sources
- Sean M. Healey & AMG Center for ALS. (2025). Sean M. Healey & AMG Center for ALS Announces New Regimen for HEALEY ALS Platform Trial With Eli Lilly and Company.
- Sironax. (2026). Sironax’s SARM1 Inhibitor SIR2501 Granted FDA Fast Track Designation in Chemotherapy-induced Peripheral Neuropathy (CIPN).
- Gerdts, J., Brace, E. J., Sasaki, Y., DiAntonio, A., & Milbrandt, J. (2015). SARM1 activation triggers axon degeneration locally via NAD⁺ destruction.
- Figley, M. D., & DiAntonio, A. (2020). The SARM1 axon degeneration pathway: control of the NAD⁺ metabolome regulates axon survival in health and disease.
- Eli Lilly and Company. (2020). Lilly Announces Agreement to Acquire Disarm Therapeutics.