# The complement system in ALS

> **NIH VA I21** · RALPH H JOHNSON VA MEDICAL CENTER · 2024 · —

## Abstract

Increasing evidence suggests that neuroinflammation in both the central nervous system and periphery
contributes to pathophysiology and disease progression of ALS. In addition, both preclinical and clinical studies
implicate a role for the complement system in the neuroinflammatory response observed in ALS, although
mechanistic details are lacking. The overall goal of this proposal is to investigate the role of complement in the
progression and pathophysiology of disease in ALS mouse models using a novel approach of complement
inhibition. Complement inhibition will be evaluated for therapeutic potential, while at the same time used as an
investigative tool to better understand the role of complement in ALS. Although clinical trials using complement
inhibitors to treat ALS have recently been announced, the approach we will investigate offers significant potential
advantages over the inhibitors entering clinical trials. The specific aims are to examine the role of complement
and the effect of targeted C3 inhibition on disease progression and survival, and to determine complement-
dependent pathophysiology and inflammatory/immune profiles during disease progression. It is expected that
data generated will provide the foundation on which to build more detailed mechanistic investigations, as well
develop novel complement-inhibitory therapeutic approaches that could be addressed in a Merit application.
There is no effective treatment for ALS, and our therapeutic strategy has the potential to be beneficial at multiple
levels by directly protecting motor neurons from complement activation in the CNS, by protecting motor end-
plates, and by potentially modifying glia-motor neuron interactions.

## Key facts

- **NIH application ID:** 10720891
- **Project number:** 5I21BX005853-02
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** Stephen Tomlinson
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10720891

## Citation

> US National Institutes of Health, RePORTER application 10720891, The complement system in ALS (5I21BX005853-02). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10720891. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*