ID: h-562d178a
Hypothesis
Anti-CD47/SIRPα Checkpoint Therapy to Enhance Phagocytic Clearance
Anti-CD47/SIRPα Checkpoint Therapy to Enhance Phagocytic Clearance.
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 4 support✗ 4 oppose
🧪 Overview
Anti-CD47/SIRPα Checkpoint Therapy to Enhance Phagocytic Clearance
🧬 Mechanism
🧬 Curated Mechanism Pathway
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:#81c784⚖️ Evidence
⚖️ Evidence Matrix4 supports4 contradicts
Supports
Anti-CD47 antibody enhances macrophage Aβ phagocytosis and reduces plaque burden
Contradicts
Anti-CD47 antibodies cause dose-limiting anemia in primates due to CD47 on erythrocytes
Contradicts
Magrolimab encountered partial clinical holds due to anemia and thrombocytopenia
Contradicts
Neuronal CD47 upregulation in response to TNF-α may represent neuroprotective attempt to prevent phagocytic elimination of stressed neurons
Contradicts
CD47 required for appropriate developmental synaptic pruning; blockade may cause synaptic dysfunction
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — CD47
No curated PDB or AlphaFold mapping for CD47 yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for CD47/SIRPα axis; target: CD47 on plaques/neurons from GTEx v10.
💉 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.
No DepMap CRISPR Chronos data found for CD47.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
No arena matches recorded yet. Browse Arenas →
📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▲ 0.0%
Volatility
Low
0.0188
Events (7d)
0
Price History
▲1.2%💾 Resource Usage
LLM Tokens
36,998
$0.1110
Total Cost
$0.1110
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| 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 |
🔮 Falsifiable Predictions (2)
pendingconf 45%
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 plaque material (synthetic Aβ42 aggregates) will increase by >50% within 48 hours compared to IgG isotype
Predicted outcome: Phagocytic index increases from baseline (~0.3) to >0.45 (50% increase) when treated with anti-CD47/SIRPα blockade
Falsification: Phagocytic index remains unchanged (<10% increase) or decreases with anti-CD47 treatment compared to vehicle/isotype control
pendingconf 35%
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 will decrease by >30% compared to vehicle-treated 5xFAD mice, as measured by in vivo [11C]PiB PET or po
Predicted outcome: Amyloid plaque burden decreases by >30% in anti-CD47 treated mice (from ~15% plaque area to <10.5%)
Falsification: No significant reduction in amyloid plaque burden (<15% decrease) or plaque load increases with anti-CD47 treatment
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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