Version history

{
  "description": "Anti-amyloid antibodies (lecanemab, donanemab) have ~0.1% brain penetrance. Engineering improved BBB transcytosis via transferrin receptor, LRP1, or novel shuttle peptides could dramatically improve efficacy.",
  "domain": "neurodegeneration",
  "status": "partially_addressed",
  "priority_score": 0.91,
  "importance_score": 0.9,
  "tractability_score": 0.75,
  "novelty_score": 0.7,
  "composite_score": 0.7002,
  "estimated_effort": "high",
  "source": "auto_detected",
  "evidence_summary": "{\"hypothesis_matches\": [{\"id\": \"h-4dd0d19b\", \"title\": \"LRP1-Dependent Tau Uptake Disruption\", \"target_gene\": \"LRP1\", \"target_pathway\": \"LRP1 receptor-mediated transcytosis\", \"match_score\": 0.7, \"composite_score\": 0.4447540669013228, \"status\": \"proposed\"}, {\"id\": \"h-959a4677\", \"title\": \"Blood-Brain Barrier SPM Shuttle System\", \"target_gene\": \"TFRC\", \"target_pathway\": \"Transferrin receptor / BBB transcytosis\", \"match_score\": 0.5, \"composite_score\": 0.5351197777903628, \"status\": \"proposed\"}, {\"id\": \"h-b948c32c\", \"title\": \"Engineered Apolipoprotein E4-Neutralizing Shuttle Peptides\", \"target_gene\": \"APOE, LRP1, LDLR\", \"target_pathway\": \"Apolipoprotein E lipid transport\", \"match_score\": 0.44, \"composite_score\": 0.4913197211784866, \"status\": \"proposed\"}, {\"id\": \"h-aa2d317c\", \"title\": \"Magnetosonic-Triggered Transferrin Receptor Clustering\", \"target_gene\": \"TFR1\", \"target_pathway\": \"Blood-brain barrier transport\", \"match_score\": 0.44, \"composite_score\": 0.4206402486635706, \"status\": \"proposed\"}, {\"id\": \"h-84808267\", \"title\": \"Synthetic Biology BBB Endothelial Cell Reprogramming\", \"target_gene\": \"TFR1, LRP1, CAV1, ABCB1\", \"target_pathway\": \"LRP1 receptor-mediated transcytosis\", \"match_score\": 0.4, \"composite_score\": 0.522661166107546, \"status\": \"proposed\"}, {\"id\": \"h-7e0b5ade\", \"title\": \"Circadian-Synchronized LRP1 Pathway Activation\", \"target_gene\": \"LRP1, MTNR1A, MTNR1B\", \"target_pathway\": \"LRP1 receptor-mediated transcytosis\", \"match_score\": 0.4, \"composite_score\": 0.48267825282356064, \"status\": \"proposed\"}, {\"id\": \"h-23a3cc07\", \"title\": \"Dual-Domain Antibodies with Engineered Fc-FcRn Affinity Modulation\", \"target_gene\": \"FCGRT\", \"target_pathway\": \"Neonatal Fc receptor / antibody transcytosis\", \"match_score\": 0.37, \"composite_score\": 0.5580009023650041, \"status\": \"proposed\"}, {\"id\": \"h-73e4340b\", \"title\": \"Pericyte Contractility Reset via Selective PDGFR-\\u03b2 Agonism\", \"target_gene\": \"PDGFRB\", \"target_pathway\": \"Blood-brain barrier transport\", \"match_score\": 0.3, \"composite_score\": 0.41877335787359243, \"status\": \"proposed\"}, {\"id\": \"h-7dfdc5d7\", \"title\": \"Mitochondrial-Cytokine Axis Modulation\", \"target_gene\": \"Mitochondrial respiratory complexes and inflammatory cytokine receptors\", \"target_pathway\": null, \"match_score\": 0.2, \"composite_score\": 0.4413417349914164, \"status\": \"proposed\"}, {\"id\": \"h-8b7727c1\", \"title\": \"Targeting Bacterial Curli Fibrils to Prevent \\u03b1-Synuclein Cross-Seeding\", \"target_gene\": \"CSGA\", \"target_pathway\": \"Bacterial curli amyloid \\u2192 \\u03b1-synuclein cross-seeding (gut-brain axis)\", \"match_score\": 0.2, \"composite_score\": 0.4361439227893742, \"status\": \"proposed\"}], \"total_matching_hypotheses\": 10, \"gap_tokens_sample\": [\"BBB\", \"LRP1\", \"amyloid\", \"anti-amyloid\", \"antibodies\", \"antibody\", \"barrier\", \"blood\", \"blood-brain\", \"brain\", \"donanemab\", \"dramatically\", \"efficacy\", \"engineering\", \"improve\"], \"updated_at\": \"2026-04-06T08:21:05.723055+00:00\"}",
  "resolution_criteria": "Resolved when: comparative evidence shows which BBB transport strategy improves antibody brain exposure beyond baseline lecanemab/donanemab penetrance while preserving target engagement and safety. Required deliverables are a cited dataset or review of transferrin receptor, LRP1, shuttle peptide, and related platforms, KG edges connecting transporters, antibody constructs, brain regions, and outcomes, and a scored hypothesis defining the minimum exposure/efficacy threshold.",
  "market_price": 0.5
}