Study Rationale: We seek to develop an oral medication that will protect dopamine neurons whose loss is thought to be the cause Parkinson’s disease (PD). Observational clinical evidence suggests that a class of calcium channel blockers called dihydropyridines can prevent or delay the onset of PD but their chemical selectivity and access to the brain are not optimal. This award will allow us to design, synthesize and test novel compounds that improve on these properties with the aim to develop a new therapy for PD.
Hypothesis: We hypothesize that selective inhibitors of the CaV1.3 voltage-gated calcium channel, optimized for brain exposure, are promising disease-modifying therapies for Parkinson’s disease.
Study Design: Lario will build on a promising high-throughput screen which generated chemical starting points to develop selective CaV1.3 inhibitors. We will conduct cycles of design, synthesis and testing to identify lead chemical series for further development as a potential neuroprotective therapy for Parkinson’s disease.
Impact on Diagnosis/Treatment of Parkinson’s disease: Published clinical observational results demonstrate impressive potential for this mechanism of disease modification. Success in our efforts would represent an important step towards a drug to slow or prevent the development of Parkinson’s disease.
Next Steps for Development: Funding from MJFF would enable a hit-to-lead series effort on this high priority target, enabling future efforts to focus on lead optimization, key efficacy studies in animal models of PD, clinical trials focused on disease prevention in prodromal and early stage PD populations.