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The study aims to id","entities":{"genes":["HNRNPA2B1/SETX/SRPK1"],"diseases":["ALS"]},"model_system":"human","_schema_version":1,"experiment_type":"clinical","primary_outcome":"Validate ALS Progression Rate Heterogeneity — mechanism and biomarker predictors","methodology_notes":"Phase 1 (Months 1-6): Recruit 400 newly diagnosed ALS patients (≤6 months from symptom onset) across 8 academic centers. Obtain informed consent and baseline assessments including ALSFRS-R, forced vital capacity, muscle strength testing, cognitive assessment (ALS-CBS), and quality of life measures. Collect blood, CSF, and urine samples for biomarker analysis. Perform whole genome sequencing and polygenic risk score calculation. Conduct baseline MRI with DTI, spectroscopy, and structural imaging. Phase 2 (Months 7-42): Monthly clinical assessments via telemedicine including ALSFRS-R, respiratory function, and adverse events. Quarterly in-person visits for biofluid collection and detailed clinical evaluation. Repeat MRI at 12 and 24 months. Analyze neurofilament light chain, phosphorylated neurofilament heavy chain, TDP-43, inflammatory cytokines, and metabolomic profiles using established assays. 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