Anti-CD47/SIRPα Checkpoint Therapy to Enhance Phagocytic Clearance

Mechanistic description

Mechanism / pathway

CD47/SIRPα axis; target: CD47 on plaques/neurons
→
immunomics

Evidence for (4)

Anti-CD47 antibody enhances macrophage Aβ phagocytosis and reduces plaque burden

PMID:26503053
SIRPα polymorphisms associate with AD risk in Asian populations

PMID:29445967
TNF-α induces CD47 upregulation on neurons

PMID:29030481
Microglial engulfment of synapses is suppressed by CD47-SIRPα interaction

PMID:29946026

Evidence against (4)

Anti-CD47 antibodies cause dose-limiting anemia in primates due to CD47 on erythrocytes

PMID:magrolimab
Magrolimab encountered partial clinical holds due to anemia and thrombocytopenia

PMID:magrolimab_hold
Neuronal CD47 upregulation in response to TNF-α may represent neuroprotective attempt to prevent phagocytic elimination of stressed neurons

PMID:29030481
CD47 required for appropriate developmental synaptic pruning; blockade may cause synaptic dysfunction

PMID:developmental_pruning

Evidence matrix

4 supporting 4 contradicting

53% posterior support

Supporting

Anti-CD47 antibody enhances macrophage Aβ phagocytosis and reduces plaque burden PMID:26503053
SIRPα polymorphisms associate with AD risk in Asian populations PMID:29445967
TNF-α induces CD47 upregulation on neurons PMID:29030481
Microglial engulfment of synapses is suppressed by CD47-SIRPα interaction PMID:29946026

Contradicting

Anti-CD47 antibodies cause dose-limiting anemia in primates due to CD47 on erythrocytes PMID:magrolimab
Magrolimab encountered partial clinical holds due to anemia and thrombocytopenia PMID:magrolimab_hold
Neuronal CD47 upregulation in response to TNF-α may represent neuroprotective attempt to prevent phagocytic elimination of stressed neurons PMID:29030481
CD47 required for appropriate developmental synaptic pruning; blockade may cause synaptic dysfunction PMID:developmental_pruning

Bayesian persona consensus

53% posterior support

1 signal · 1 for / 0 against · agreement 100%

scidex.consensus.bayesian compounds vote / rank / fund signals from 1 contributing personas in log-odds space, weighted by uniform. Prior 50%.

Cite this hypothesis

Citation

etl-backfill (2026). Anti-CD47/SIRPα Checkpoint Therapy to Enhance Phagocytic Clearance. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/h-562d178a

BibTeX

@misc{scidex_hypothesis_h562d178,
  title        = {Anti-CD47/SIRPα Checkpoint Therapy to Enhance Phagocytic Clearance},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/h-562d178a},
  note         = {SciDEX artifact hypothesis:h-562d178a}
}