{"artifact":{"id":"experiment-exp-wiki-experiments-anti-tau-therapy-failure-psp","artifact_type":"experiment","entity_ids":null,"title":"Anti-Tau Therapy Failure Mechanism in PSP — Why Clinical Trials Have Not Succeeded","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"wiki","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.903578Z"},"summary":"# Anti-Tau Therapy Failure Mechanism in PSP — Why Clinical Trials Have Not Succeeded\n## Background and Rationale\nThis experiment addresses a critical therapeutic failure in neurodegeneration: why anti-tau therapies have consistently failed in Progressive Supranuclear Palsy (PSP) clinical trials despite compelling preclinical rationale. Multiple high-profile trials including gosuranemab (ABBV-8E12) in the TANGOS study and tilavonemab have failed to demonstrate clinical efficacy in PSP patients, d","entities":{"genes":["PSP"],"diseases":["ALS"]},"model_system":"human","_schema_version":1,"experiment_type":"clinical","primary_outcome":"Validate Anti-Tau Therapy Failure Mechanism in PSP — Why Clinical Trials Have Not Succeeded","methodology_notes":"**Phase 1: Patient Cohort Assembly and Characterization (Months 1-6)**\n• Recruit 200 PSP patients from completed anti-tau trials (gosuranemab, tilavonemab) and 100 treatment-naive PSP patients\n• Collect comprehensive clinical data: PSP-RS scores, MDS-UPDRS-III, SEADL, CGI-S at baseline and follow-up timepoints\n• Perform detailed neuropathological analysis on available autopsy samples (n=50) with tau burden quantification\n• Conduct CSF biomarker analysis: total tau, phospho-tau (pT181, pT217, pT231), neurofilament light, and MTBR-tau243\n• Analyze plasma biomarkers using Simoa platform for tau species and neuroinflammatory markers\n\n**Phase 2: Pharmacokinetic and Target Engagement Analysis (Months 4-10)**\n• Measure antibody concentrations in CSF and plasma samples using validated ELISA assays\n• Assess blood-brain barrier penetration ratios for each therapeutic antibody\n• Quantify tau target engagement using proximity ligation assays and tau conformation-specific antibodies\n• Evaluate anti","replication_status":"conflicting","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.903584","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID 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