Premature investment. The Expert identifies that no validated partial CSF1R agonist exists—creating partial agonism for a receptor kinase requires allosteric modulators with precise cooperativity values that are chemically non-trivial. Orion Corporation's LIGAMENT trial (CSF1R inhibitor in ALS) will read out in 2025 and is critical; if inhibition worsens disease, partial agonism logic is validated, but if inhibition helps, the entire axis is challenged. TREM2 antibodies in ALS (Alector) provide parallel development path.
Curated pathway from expert analysis
flowchart TD
A["Testosterone/ANDROGEN RECEPTOR Axis<br/>Neuronal Androgen Binding"]
B["AR Nuclear Translocation<br/>Coactivator Recruitment and Hormonal Ligand"]
C["TM4SF5 and CD82 Expression<br/>Senescent Cell Surface Marker Induction"]
D["Senolytic Target Engagement<br/>p53-Dependent Apoptosis in SASP Cells"]
E["Inflammatory Niche Remodeling<br/>SASP Factor Clearance"]
F["Neurodegenerative Niche Improvement<br/>Reduced Inflammatory Tone"]
A --> B
B --> C
C --> D
D --> E
E --> F
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for CSF1R Partial from GTEx v10.
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.
No DepMap CRISPR Chronos data found for CSF1R Partial.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF ALS patients treated with TREM2-activating antibodies (AL001 or AL002, Alector Phase 2 trials) show statistically significant reduction or stabilization of cerebrospinal fluid neurofilament light c | CSF NfL levels decrease by ≥20% from baseline or remain ≤10% above baseline in TREM2 antibody treatment group vs ≥40% increase in placebo group at 12 months, wi | — no observation — | pending | 0.25 |
| IF ALS patients receiving CSF1R inhibitor (PLX3007) in the Orion LIGAMENT trial demonstrate ≥20% faster disease progression (ALSFRS-R slope increase) compared to placebo over 24 weeks, THEN this outco | ALSFRS-R total score decline rate of ≥1.2 points/month in treatment arm vs ≤1.0 points/month in placebo arm (20% difference), with corresponding plasma neurofil | — no observation — | pending | 0.35 |