Idea ID: inv006-biomarker-nfl-rapid
Target: Neurofilament Light Chain (NfL) axis
Indication: ALS, Parkinson's Disease, Alzheimer's Disease
Approach: NfL-lowering therapy for patients with elevated NfL indicating rapid progression
Rationale: Elevated NfL predicts faster disease progression; lowering NfL may reflect neuroprotection
Neurofilament Light Chain is a structural protein released when axons damage:
| Disease | Finding | Clinical Implication |
|---|---|---|
| ALS | CSF NfL predicts survival (median 2.1 yrs if high) | Benatar et al., 2018 |
| PD | Baseline NfL predicts cognitive decline | Mollenhauer et al., 2021 |
| AD | NfL correlates with atrophy rate | Mattsson et al., 2019 |
| ALS | NfL responds to treatment (tofersen) | FDA Tofersen approval |
Patients with elevated NfL (>75th percentile) have "rapid progression phenotype." Targeting this subgroup:
Enrichment criteria:
Candidates:
| Approach | Target | Stage |
|---|---|---|
| NfL-guided | This approach | Concept |
| Tofersen | SOD1 | Approved (ALS) |
| CNTF | CNTF | Phase 1/2 |
| Sarm1 inhibitor | SARM1 | Preclinical |