Study Rationale: Parkinson’s disease (PD) is associated with a loss of mitochondrial function and increased inflammation. A dual-action drug candidate, KLS-13019, both protects mitochondria from chemical stress and displays anti-inflammatory properties in cells and in rodents that develop a PD-like condition after exposure to environmental toxins. The protective properties of our compound are related to its interaction with NCX-1, a mitochondrial protein that promotes neuronal survival, and GPR55, a mitochondrial protein that plays a role in motor coordination. Both of these proteins are present in a part of the brain that is damaged in PD, making them attractive targets for therapeutic intervention.
Hypothesis: We hypothesize that exposure to environmental toxins can produce an inflammatory substance that interacts with GPR55, contributing to the loss of a brain chemical that controls muscle coordination, and that KLS-13019 can block the inflammatory responses produced by this substance or by a genetic mutation found in people with PD.
Study Design: We will test KLS-13019 in mice that have been treated with a genetically mutated form of alpha-synuclein that is found in people with PD. We will perform muscle coordination tests and measure the degeneration and inflammation in brain regions relevant to PD. Together these tests will determine whether the drug candidate can prevent and reverse the effects produced by this mutant form of alpha-synuclein.
Impact on Diagnosis/Treatment of Parkinson’s disease: This project will test a novel drug candidate for its potential to prevent and reverse the impairment of muscle coordination and abnormal brain chemistry in a preclinical PD model.
Next Steps for Development: KLS-13019 is currently being tested for safety with support from the National Institutes of Health for another therapeutic use.