ID: h-0c78964fbd
Hypothesis

Pharmacologic SARM1 blockade to prevent Wallerian degeneration after axotomy

SARM1 is the executioner of axonal degeneration through its NMN hydrolase activity, and pharmacologic inhibition completely blocks Wallerian degeneration in acute injury models.
🧬 SARM1🩺 neurodegeneration🎯 Composite 66%💱 $0.58▼10.9%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates 3 support 2 oppose
✓ All Quality Gates Passed
Mechanistic 0.60 (15%) Evidence 0.70 (15%) Novelty 0.65 (12%) Feasibility 0.68 (12%) Impact 0.62 (12%) Druggability 0.85 (10%) Safety 0.58 (8%) Competition 0.60 (6%) Data Avail. 0.65 (5%) Reproducible 0.62 (5%) KG Connect 0.50 (8%) 0.660 composite

🧪 Overview

SARM1 is the executioner of axonal degeneration through its NMN hydrolase activity, and pharmacologic inhibition completely blocks Wallerian degeneration in acute injury models. Tool compounds (D-77, NVG-298) demonstrate in vivo efficacy in CIPN models, and Disarm Therapeutics has a Phase 1 program. The primary translational challenge is that ALS involves chronic multi-system failure rather than acute axotomy; SOD1 mouse models show only modest benefits from SARM1 deletion. Pursuing CIPN as an initial indication de-risks before ALS expansion.

🧬 Mechanism

No curated mechanism pathway recorded for this hypothesis.

⚖️ Evidence

⚖️ Evidence Matrix3 supports2 contradicts
Supports
SARM1 knockout completely blocks Wallerian degeneration
Supports
SARM1 inhibitors protect axons in CIPN models
Supports
SARM1 inhibitor in Phase 1 for peripheral neuropathy
Contradicts
SARM1 KO x SOD1 mice show modest NMJ preservation but no survival benefit
Contradicts
SARM1 KO mice show impaired T-cell activation
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — SARM1

No curated PDB or AlphaFold mapping for SARM1 yet. Search RCSB →

💉 Clinical Trials

No clinical trials data linked to this hypothesis yet.

No curated ClinVar variants loaded for this hypothesis.

Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.

🔍 Search ClinVar for SARM1 →

No DepMap CRISPR Chronos data found for SARM1.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

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📊 Market Indicators

7d Trend
Falling
7d Momentum
▼ 1.6%
Volatility
Low
0.0017
Events (7d)
4
Price History
▼10.9%

💾 Resource Usage

No resource usage or linked notebooks recorded for this hypothesis yet.

Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
sourcev1_phase_c_backfill
origin_typedebate_synthesizer
_schema_version1
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting 0 contradicting 0 neutral
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