{"artifact":{"id":"experiment-exp-wiki-experiments-combination-therapy-sequencing-pd","artifact_type":"experiment","entity_ids":null,"title":"Combination Therapy Sequencing in Parkinson's Disease","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":"2026-04-16T01:00:16.904625Z"},"summary":"# Combination Therapy Sequencing in Parkinson's Disease\n## Background and Rationale\nThis translational validation study systematically evaluates optimal sequencing and combination strategies for disease-modifying therapies in Parkinson's disease, addressing the critical clinical need for rational polytherapy approaches. The experiment employs both preclinical models and human biomarker studies to determine synergistic combinations of neuroprotective agents targeting complementary pathways includ","entities":{"genes":["ADRA2A/DNMT1/DRD2"],"diseases":["Parkinson's Disease"]},"model_system":"human","_schema_version":1,"experiment_type":"validation","primary_outcome":"Identification of at least three synergistic drug combinations showing >30% greater neuroprotection than individual agents in α-synuclein transgenic mice, with validated biomarker signatures predicting human response in ex vivo patient samples.","methodology_notes":"**Phase 1: Patient Recruitment and Baseline Assessment (Weeks 1-4)**\n• Recruit 240 Parkinson's disease patients (Hoehn & Yahr stages 2-3) from multiple clinical centers\n• Obtain informed consent and verify inclusion criteria: age 50-75, confirmed PD diagnosis >2 years, stable on levodopa ≥3 months\n• Exclude patients with atypical parkinsonism, dementia (MoCA <26), or recent deep brain stimulation\n• Randomize patients into 4 groups (n=60 each): Group A (levodopa→dopamine agonist→MAO-B inhibitor), Group B (dopamine agonist→levodopa→MAO-B inhibitor), Group C (MAO-B inhibitor→levodopa→dopamine agonist), Group D (standard care control)\n• Conduct baseline assessments: UPDRS Parts I-IV, Parkinson's Disease Questionnaire-39 (PDQ-39), levodopa equivalent daily dose (LEDD), and motor fluctuation diary\n\n**Phase 2: First Treatment Intervention (Weeks 5-16)**\n• Initiate first therapy according to randomization sequence\n• Titrate medications over 4 weeks to optimal therapeutic dose based on clinical","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.904631","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID 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