AAV-LRRK2 IND-Enabling Study Design

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AAV-LRRK2 IND-Enabling Study Design

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experiment Created: 2026-04-02T10:01:41 By: crosslink-v2 Quality: 67% ✓ SciDEX ID: experiment-exp-wiki-experiments-aav-lrrk

🧫 Experiment Protocol Clinicalproposed

SUMMARY

# AAV-LRRK2 IND-Enabling Study Design ## Background and Rationale This IND-enabling study represents a critical translational milestone for AAV-mediated LRRK2 gene therapy in Parkinson's disease, building upon successful AAV serotype comparison studies. LRRK2 (Leucine-rich repeat kinase 2) mutations account for approximately 5-15% of familial Parkinson's cases and represent a validated therapeutic target. The study aims to generate comprehensive preclinical safety, biodistribution, and efficacy

METHODOLOGY NOTES

Phase 1: GLP Toxicology Studies (Months 1-6) - Conduct dose-escalation studies in 48 cynomolgus macaques (n=8 per group, 6 dose levels) via intrathecal or intraventricular AAV-LRRK2 administration. Doses: 1×10^11, 3×10^11, 1×10^12, 3×10^12, 1×10^13, 3×10^13 vg/animal. Phase 2: Biodistribution Analysis (Months 2-8) - Quantify vector distribution in CNS and peripheral tissues using qPCR at 4, 12, and 24 weeks post-injection in 36 animals (n=6 per timepoint per dose group). Phase 3: Immunogenicity Assessment (Months 1-12) - Monitor AAV capsid and LRRK2 transgene-specific immune responses via ELISA, ELISpot, and neutralizing antibody assays in all animals at baseline, 2, 4, 8, 12, 24, and 48 weeks. Phase 4: Efficacy Studies (Months 6-18) - Evaluate motor function using automated gait analysis, rotarod performance, and fine motor tasks in MPTP-lesioned macaques treated with therapeutic doses. Assess dopaminergic neuron preservation via PET imaging and post-mortem immunohistochemistry. Phase

▸Metadatasource: {'type': 'manual', 'source_name': 'wiki'

source	{'type': 'manual', 'source_name': 'wiki', 'extracted_by': 'backfill_v1', 'extraction_date': '2026-04-16T01:00:16.899267Z'}
summary	# AAV-LRRK2 IND-Enabling Study Design ## Background and Rationale This IND-enabling study represents a critical translational milestone for AAV-mediated LRRK2 gene therapy in Parkinson's disease, buil
entities	{'genes': ['AAV'], 'diseases': ["Parkinson's Disease"]}
model_system	human
_schema_version	1
experiment_type	clinical
primary_outcome	Validate AAV-LRRK2 IND-Enabling Study Design
methodology_notes	Phase 1: GLP Toxicology Studies (Months 1-6) - Conduct dose-escalation studies in 48 cynomolgus macaques (n=8 per group, 6 dose levels) via intrathecal or intraventricular AAV-LRRK2 administration. Do
replication_status	single_study
extraction_metadata	{'backfill_at': '2026-04-16T01:00:16.899276', 'needs_review': True, 'extraction_notes': 'Backfilled from wiki source (no PMID available)', 'extraction_confidence': 0.4}

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AAV-LRRK2 IND-Enabling Study Design

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