Study Rationale:
Mitochondrial dysfunction has a prominent role in the process of Parkinson’s disease (PD). Mutations in at least seven genes are known to underlie PD, most of them encode proteins that impact mitochondrial function and clearance, cellular oxidative stress or redox balance. This project aims to repurpose KH176, a molecule currently under development for the treatment of mitochondrial disease, as a potential therapeutic for PD.
Hypothesis:
We hypothesize that KH176 will act as a neuroprotective agent by restoring or preventing the cellular redox imbalance, particularly in dopaminergic neurons, and ultimately prevent and/or delay the onset and/or progression of Parkinson’s disease.
Study Design:
We will study the pharmacokinetic and therapeutic efficacy of KH176 in neurodegenerative PD models with known underlying mitochondrial implication. First, we will perform a study to optimize the dosing scheme (frequency and concentration) for long-term oral treatment. Our team will evaluate therapeutic efficacy on behavioral outcome measures such as impaired motor behavior and gait abnormalities. Furthermore, we will examine the effect of KH176 on the loss of dopaminergic neurons, redox balance and oxidative stress markers.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
We believe KH176 has great potential as a repositioned drug for PD, to alter the course of disease progression. We hope to find marked disease-modifying therapeutic effects on one or more outcome measures.
Next Steps for Development:
A successful outcome of this study will allow KH176 to enter preparations for a Phase II clinical trial in PD patients, with the ultimate goal to develop a novel therapeutic for PD.
Additional Support:
The Michael J. Fox Foundation would like to acknowledge the generous contribution of the Demoucelle Parkinson Charity as a lead supporter providing funding for this project.