GLP-1 Agonist Responder Prediction Study — Precision Medicine for Neuroprotection in PD

SUMMARY

# GLP-1 Agonist Responder Prediction Study — Precision Medicine for Neuroprotection in PD ## Background and Rationale This precision medicine study addresses a critical knowledge gap in Parkinson's disease therapeutics by developing and validating biomarker-based prediction models for GLP-1 agonist response. The heterogeneous results from recent lixisenatide trials underscore the urgent need to identify which early-stage PD patients will benefit from these potentially neuroprotective therapies.

METHODOLOGY NOTES

## **Phase 1: Patient Recruitment and Stratification (Months 1-6)** Recruit 240 early-stage PD patients (Hoehn & Yahr stages 1-2, diagnosed ≤3 years) from 8 movement disorder centers. Inclusion: age 50-75, stable dopaminergic therapy ≥3 months, MoCA ≥24. Exclusion: diabetes, prior GLP-1 agonist use, significant comorbidities. Collect baseline demographics, genetic variants (APOE, GBA, LRRK2), metabolic markers (HbA1c, insulin resistance), neuroinflammatory markers (IL-6, TNF-α, CRP), and neuroimaging biomarkers (DaTscan SPECT for dopamine transporter binding). ## **Phase 2: Comprehensive Baseline Assessment (Months 3-8)** Conduct standardized clinical assessments: MDS-UPDRS Parts I-IV, PDQ-39, cognitive battery (MoCA, semantic fluency, Trail Making), olfactory testing (UPSIT), REM sleep behavior disorder questionnaire, and autonomic function tests. Perform advanced neuroimaging including structural MRI (cortical thickness, subcortical volumes), diffusion tensor imaging (white matter i