Study Rationale: Dysfunction in energy-producing structures called mitochondria is a crucial driver of the initiation and progression of Parkinson’s disease (PD). Mitochondria in the cells of people with PD show a variety of deficits in metabolism as well as signaling. Several of these deficits appear very early in disease progression. Rather than focusing on symptoms that appear later in the course of the disease, targeting early mitochondrial deficits offers a better opportunity for developing disease-modifying therapies for many types of PD.
Hypothesis: We hypothesize that improving several key mitochondrial functions simultaneously will lead to an improvement or reversal of pathologies seen in cells and neurons from people with PD, providing a potential disease-modifying therapeutic.
Study Design: We will design and test small molecules for their ability to improve mitochondrial function in cells and neurons from people with PD or in cells that replicate the deficits found in PD. Based on the results of these experiments, we will further modify and optimize these candidates to make them suitable for clinical trials. We are also looking for biomarkers or changes caused by our compounds which could be used to monitor our compound’s effect on the impact on our target and its effectiveness at ameliorating symptoms in people with PD in a clinical trial.
Impact on Diagnosis/Treatment of Parkinson’s disease: Mitochondrial dysfunction is implicated in familial and sporadic (or idiopathic) cases of PD. Based on its mechanism of action, our drug has the potential to affect multiple forms of PD and to be disease-modifying in both early and later stages of the disease by targeting a nexus of PD pathology.
Next Steps for Development: If our project is successful, Lucy Therapeutics will have a candidate drug with early toxicological data suitable for Phase 1 clinical entry and we will have identified biomarkers which could help select participants for clinical trials.