Study Rationale: Our aim is to develop an oral medication that will protect the dopamine neurons whose loss is thought to be the cause Parkinson’s disease (PD). Evidence suggests that excessive levels of calcium make these dopamine neurons vulnerable to environmental and genetic stresses. This grant will allow us to test in preclinical models and in nerve cells derived from people with PD whether compounds designed to inhibit a key pathway leading to calcium accumulation in these vulnerable neurons can prevent PD.
Hypothesis: We hypothesize that a potential drug designed to inhibit a specific ion channel in brain (CaV2.3) can improve disease-related phenotypes in cells derived from people with PD and that such a drug can prevent PD symptoms and neuron loss in two preclinical models of PD.
Study Design: Lario Therapeutics has developed advanced inhibitors of the CaV2.3 ion channel that have profiles of a potential drug; these inhibitors will be tested in proof-of-concept studies in patient-derived cell lines from genetic forms of PD and in two different preclinical PD models. These studies could provide the basis for moving a potential drug into further clinical development.
Impact on Diagnosis/Treatment of Parkinson’s disease: Success in these experiments would represent an important step towards a drug to slow or prevent the development of PD.
Next Steps for Development: Positive results for one of the tested compounds would form the basis for entering into a process that could culminate in filing an Initial New Drug Application in approximately 12 to 18 months; this authorization would enable our most promising drug candidate to be tested in clinical trials.