SBIR Phase I: Development and Validation of a Novel Parkinson's Disease Drug Discovery Platform Using Patient-Derived Midbrain Organoids

The broader impact of this Small Business Innovation Research (SBIR) Phase I project spans several fronts, starting with advancements in public health and welfare. The project goal is to reduce risks in clinical translation and expedite the development of crucial therapies for Parkinson's disease. Additionally, the highly scalable nature of the proposed platform offers the long-term potential to extend its application to other complex brain disorders and therapeutic domains. The platform will guide therapeutic candidate discovery, stratify patient selection and refine clinical trial endpoints. Beyond health, the project impact extends to the economic competitiveness of the US. For example, by providing therapies that can help address the challenges people with neurological disorders face in the workforce, the developed product will contribute to operational efficiency, reduce healthcare costs, and boost workforce productivity. The commitment to accelerating therapeutic development also fuels innovation, attracting investments and creating high-value jobs, solidifying the US as a global leader in healthcare innovation. Furthermore, the project team actively promotes partnerships between patient foundations, academia, and drug developers in the biopharma industry. The proposed project addresses the urgent need for effective disease-modifying therapies for Parkinson's disease. There are no approved disease-modifying therapies for Parkinson's disease due to challenges, including the lack of reliable animal models that accurately predict human efficacy, and a poor understanding of the genetic, environmental and lifestyle factors contributing to dopamine neuron degeneration. To overcome these hurdles, an all-in-human Parkinson's disease drug discovery platform will be developed. This approach utilizes familial Parkinson's disease patient-derived midbrain organoid disease models, biomarker-based screening endpoints, and advanced data analytics to identify disease-modifying therapeutics that halt, prevent, or reverse dopamine neuron degeneration. This platform is positioned as a game-changer in the discovery of impactful Parkinson's disease treatments. The core innovations of the approach include patient-derived stem cells capturing human disease biology at the earliest drug development stages, human-first drug discovery reducing reliance on animal models, scalability and reproducibility of organoid production, robust and reproducible quantification of disease-specific phenotypes, and screening compatible with various therapeutic modalities. The focus on genetically validated targets and converging pathways in sporadic Parkinson's disease aims to de-risk clinical translation, reduce costs, and accelerate the discovery of transformative Parkinson's disease therapies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.