DNA Damage Repair Deficiency Validation Study in Parkinson's Disease

SUMMARY

# DNA Damage Repair Deficiency Validation Study in Parkinson's Disease ## Background and Rationale DNA damage accumulation represents a fundamental driver of neurodegeneration in Parkinson's disease (PD), with emerging evidence suggesting that impaired DNA repair mechanisms create a cascade of cellular dysfunction specifically targeting dopaminergic neurons in the substantia nigra. The brain's high metabolic demands and limited regenerative capacity make neurons particularly vulnerable to oxidat

METHODOLOGY NOTES

**Phase 1: Patient Recruitment and Baseline Assessment (Weeks 1-8)** • Recruit 180 participants: 120 Parkinson's disease patients (Hoehn-Yahr stages 1-3) and 60 age-matched healthy controls • Inclusion criteria: PD diagnosis per MDS criteria, age 50-75 years, stable medications ≥3 months • Exclusion criteria: atypical parkinsonism, dementia (MoCA <24), concurrent malignancy, prior PARP inhibitor exposure • Obtain informed consent and collect demographic data, medical history, and concomitant medications • Perform comprehensive clinical assessments: MDS-UPDRS Parts I-IV, Hoehn-Yahr staging, MoCA, PDQ-39 • Collect baseline biosamples: 20mL blood for PBMC isolation, 10mL cerebrospinal fluid (optional substudy, n=40) **Phase 2: DNA Damage Repair Functional Assays (Weeks 9-12)** • Isolate PBMCs using Ficoll density gradient centrifugation within 4 hours of collection • Perform comet assay on fresh PBMCs: baseline DNA damage and repair kinetics at 0, 2, 4, 8, 24 hours post-H2O2 treatment (1