Evidence indicates that mitochondrial dysfunction is a significant contributor to Parkinson’s disease, with the majority of patients exhibiting a shared defect in the processing of the mitochondrial protein Miro1. Most pathological and genetic pathways known to be associated with Parkinson's converge at Miro1, highlighting its importance. Correcting the Miro1 processing defect, either through genetic knockdown or pharmacologic inhibition, stops disease progression in Parkinson's models. Building upon the work in the initial grant, CuraX has identified a second small-molecule compound family to develop in parallel, which corrects the Miro1 defect. In this study, the team will to optimize, validate and advance this second family of compounds into models of Parkinson's.
We hope that optimizing and developing this second compound family and its associated target will produce therapies that slow or stop the progression of Parkinson's.
We will conduct medicinal chemistry on the second compound family. The most promising compounds in these initial screens will undergo additional medicinal chemistry optimization for oral bioavailability, brain penetrance and other drug-like properties. We will evaluate the best compounds in models of Parkinson's in a three-stage process. First, we will test models of Parkinson's to establish if the Miro1 defect seen in Parkinson's patients is also present in the model. In models with a demonstrated Miro1 defect, we will evaluate select compounds for their ability in vivo to correct the Miro1 defect. Finally, we will evaluate the preferred compound for its ability to improve Parkinson's pharmacology and the Miro1 defect in the model.
Impact on Diagnosis/Treatment of Parkinson’s disease:
We expect to identify a compound with demonstrated efficacy in a model of Parkinson's to move to regulatory studies required for clinical development. This compound would be one of the first targeting a specific mitochondrial mechanism to advance to the clinic.
Next Steps for Development:
The team expects to advance its compound(s) through required regulatory studies, followed by the filing of an investigational new drug (IND) application to the U.S. Food and Drug Administration to enable Phase I clinical trials.