Seattle-based Shape Therapeutics has received a research grant from The Michael J. Fox Foundation for Parkinson's Research to fund IND-enabling studies of SHP-201, its lead Parkinson's gene therapy candidate, the company announced July 29. The award, made through MJFF's Parkinson's Disease Therapeutics Pipeline Program, will support pharmacology, pharmacokinetic, biodistribution, and toxicology studies across a range of doses ahead of a planned IND submission. No timeline for that filing was disclosed.
SHP-201 combines Shape's blood-brain barrier-crossing AAV capsid with an RNA-editing payload based on its RNAfix technology, designed to recruit endogenous ADAR enzymes to perform site-directed editing of the SNCA transcript and reduce alpha-synuclein production. Delivered as a single intravenous infusion, the approach is intended to achieve durable, brain-wide alpha-synuclein reduction, including in the substantia nigra and other deep subcortical regions most affected in Parkinson's disease. In a pilot non-clinical study, intravenous delivery demonstrated on-target activity throughout the brain, with the highest activity reported in those deep subcortical regions. No quantitative efficacy or safety data were disclosed.
The absence of any approved disease-modifying therapy for Parkinson's disease frames the broader context for programs targeting alpha-synuclein. Roche and Prothena's prasinezumab, an anti-alpha-synuclein monoclonal antibody, narrowly missed its primary endpoint in the Phase IIb PADOVA trial — reporting a hazard ratio of 0.84 (95% CI: 0.69–1.01; p=0.0657) for motor progression — before Roche advanced the program to Phase III in mid-2025. That near-miss illustrates the difficulty of detecting a clinical signal in early Parkinson's disease trials, particularly for disease-modifying endpoints. On the AAV gene therapy side, Voyager Therapeutics and Neurocrine Biosciences' VY-AADC (NBIb-1817) demonstrated symptomatic benefit in Phase I but encountered a clinical hold due to MRI abnormalities, a safety precedent relevant to any intravenously delivered CNS gene therapy program. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.