SUMMARY
# GLP-1 Agonist Neuroprotection Mechanism in PD
## Background and Rationale
Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration in the substantia nigra, leading to motor dysfunction and cognitive decline. Recent preclinical evidence suggests that GLP-1 receptor agonists, originally developed for diabetes treatment, exhibit neuroprotective properties through multiple mechanisms including anti-inflammatory effects, mitochondrial stabilization, and promotion of n
METHODOLOGY NOTES
Phase 1 (Weeks 0-4): Recruit 120 early-stage PD patients (Hoehn-Yahr stages 1-2.5). Obtain informed consent and conduct baseline assessments including MDS-UPDRS, Montreal Cognitive Assessment, DaTscan SPECT imaging, and blood collection for biomarker analysis (inflammatory cytokines IL-1β, TNF-α, IL-6; oxidative stress markers 8-OHdG, MDA; GLP-1 pathway components). Phase 2 (Weeks 4-52): Randomize participants 1:1 to subcutaneous exenatide 2mg weekly or matched placebo. Conduct safety monitoring every 4 weeks with adverse event documentation and vital signs. Perform interim assessments at weeks 12, 24, and 36 including MDS-UPDRS Part III, cognitive testing, and biomarker sampling. Phase 3 (Week 52): Conduct comprehensive endpoint evaluation including repeat DaTscan SPECT, full clinical battery, and biomarker analysis. Perform CSF sampling in consenting participants (target n=60) for neuroinflammatory markers and α-synuclein species. Phase 4 (Weeks 52-56): Complete safety follow-up and