{"artifact":{"id":"experiment-exp-wiki-experiments-sca-disease-modifying-therapy","artifact_type":"experiment","entity_ids":null,"title":"Spinocerebellar Ataxia (SCA) Disease-Modifying Therapy Development","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":"2026-04-16T01:00:16.906206Z"},"summary":"# Spinocerebellar Ataxia (SCA) Disease-Modifying Therapy Development\n## Background and Rationale\nThis validation study aims to develop and test disease-modifying therapies for spinocerebellar ataxias (SCAs), a group of inherited neurodegenerative disorders characterized by progressive cerebellar degeneration and motor dysfunction. The research addresses the current lack of effective treatments for SCAs by targeting key pathogenic mechanisms including protein misfolding, mitochondrial dysfunction","entities":{"genes":["SCA"],"diseases":["Neurodegeneration"]},"model_system":"human","_schema_version":1,"experiment_type":"validation","primary_outcome":"Reduction in ataxin protein aggregation and improvement in cerebellar neuron survival in patient-derived iPSC models treated with lead therapeutic candidates.","methodology_notes":"**Phase 1: Patient Recruitment and Baseline Assessment (Months 1-3)**\n• Recruit 180 genetically confirmed SCA patients (SCA1, SCA2, SCA3, SCA6) across multiple centers\n• Include patients with SARA scores 8-25, disease duration 2-10 years\n• Exclude patients with other neurological conditions or significant comorbidities\n• Perform comprehensive neurological assessment: SARA, ICARS, 8MW, 9HPT, PATA rate\n• Conduct baseline MRI volumetry (cerebellum, brainstem, cortical regions)\n• Collect CSF samples for biomarker analysis (neurofilament light, tau, polyQ aggregates)\n• Obtain skin fibroblasts for iPSC generation and cellular assays\n• Randomize patients 1:1:1 to autophagy enhancer (trehalose 90g/day), polyQ aggregation inhibitor (EGCG 800mg/day), or placebo\n\n**Phase 2: Treatment Intervention (Months 4-18)**\n• Administer oral medications twice daily with standardized meal timing\n• Monthly safety assessments: liver function, renal function, complete blood count\n• Quarterly efficacy assessments","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.906213","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID available)","extraction_confidence":0.4}},"created_at":"2026-04-02T10:01:41.825940-07:00","updated_at":"2026-04-16T01:00:16-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":"2026-04-02T10:01:41.825940-07:00","citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":"ok","contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"c9c6787d-fe6c-4764-b9e8-1d0ab689f1c0","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"crosslink-v2"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"wiki-technologies-rna-editing-therapeutics","link_type":"related","strength":0.63,"evidence":"Reverse: 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