Anti-CD47/SIRPα Checkpoint Therapy to Enhance Phagocytic Clearance
Curated pathway from expert analysis
flowchart TD
A["CD47 Expression<br/>Amyloid Plaques and Neurons"]
B["SIRPalpha Engagement<br/>Microglial Inhibitory Receptor"]
C["SHIP1 and SHP1 Activation<br/>Phagocytic Inhibitory Cascade"]
D["Phagocytosis Suppression<br/>Reduced Amyloid Clearance"]
E["Amyloid Accumulation<br/>Plaque Burden Increase"]
F["Anti-CD47 Antibody<br/>Checkpoint Blockade Therapy"]
G["SIRPalpha Disengagement<br/>Inhibitory Signal Released"]
H["Microglial Phagocytosis<br/>Enhanced Amyloid Clearance"]
A --> B
B --> C
C --> D
D --> E
F -.->|"blocks"| A
F --> G
G -.->|"releases"| D
G --> H
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#1b5e20,stroke:#81c784,color:#81c784
style H fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for CD47 yet. Search RCSB →
Median TPM across 13 brain regions for CD47/SIRPα axis; target: CD47 on plaques/neurons 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 CD47.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF 5xFAD transgenic mice (Alzheimer's disease model) receive intravenous administration of anti-CD47 antibody (0.5 mg/kg, biweekly for 4 weeks), THEN cortical and hippocampal amyloid plaque burden wil | Amyloid plaque burden decreases by >30% in anti-CD47 treated mice (from ~15% plaque area to <10.5%) | — no observation — | pending | 0.35 |
| IF primary human macrophages or iPSC-derived microglia are treated with blocking anti-CD47 antibody (or SIRPα-Fc fusion protein) ex vivo, THEN phagocytic uptake of fluorescently-labeled neuritic plaqu | Phagocytic index increases from baseline (~0.3) to >0.45 (50% increase) when treated with anti-CD47/SIRPα blockade | — no observation — | pending | 0.45 |