How the protein SARM1 drives nerve fiber loss in ALS and related neuropathies
The role of SARM1 in neuroinflammation-mediated axonal damage
This project explores whether stopping SARM1 activity and the immune response that clears stressed nerve fibers can slow nerve damage in ALS and certain peripheral neuropathies.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11262851 on NIH RePORTER |
What this research studies
You would hear that researchers are focusing on SARM1, a protein that can trigger local metabolic collapse in damaged nerve fibers and lead to degeneration. They use a human-based disease model from people with NMNAT2 mutations alongside animal and lab experiments to see how SARM1 causes macrophages to attack stressed axons. The team has found that removing macrophages or blocking an 'eat-me' signal called lyso-PS delays motor decline in their model. The project tests genetic and drug-like approaches to stop SARM1-driven macrophage recruitment and lyso-PS exposure to try to preserve axons and function.
Who could benefit from this research
Good fit: Ideal candidates for future participation would include people with ALS or progressive peripheral neuropathies, particularly individuals with NMNAT2-related early-onset polyneuropathy who could provide samples or join trials.
Not a fit: Patients with very advanced, end-stage nerve loss or conditions where degeneration is not driven by SARM1-related mechanisms are unlikely to benefit from these approaches.
Why it matters
Potential benefit: If successful, this work could lead to treatments that prevent or slow axon loss and improve motor function in ALS and some peripheral neuropathies.
How similar studies have performed: Previous genetic and animal studies support SARM1 as a key driver of axon loss and show that blocking macrophage activity or SARM1-related signals can delay degeneration, but clinical translation is still early.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Milbrandt, Jeffrey D — Washington University
- Study coordinator: Milbrandt, Jeffrey D
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.