Study Rationale: The mitochondrial protein Miro1 fails to be degraded and this defect impairs mitophagy in more than 90% of all Parkinson’s disease (PD) patients of both genetic and sporadic forms. Recent studies have also shown that asymptomatic children of PD parents with known genetic risk factors display a defect in Miro1 degradation. Further, biostatistical data suggests that the degree of the Miro1 defect correlates with the cognitive features of disease progression. Together, these data suggest that the presence of a Miro1 defect will serve as an important early diagnostic and prognostic biomarker of PD to accelerate drug discovery, drug development and clinical trials.
Hypothesis: A Miro1 test in white blood cells could help detect mutations demonstrated in PD patient skin cells and neurons, and this test can be used as a tool for longitudinal patient studies and a clinical biomarker in clinical trials.
Study Design: AcureX will use established assays to translate findings from patient skin cells into an assay using patient white blood cells. Taking a staged approach, we will validate the Miro1 assay using white blood cells from patients and matched healthy control subjects. Analytic and measurement techniques will be evaluated, and the assay will be optimized for use in future large-scale and clinical studies.
Impact on Diagnosis/Treatment of Parkinson’s disease: Development of a Miro1 assay in white blood cells as a Parkinson’s disease biomarker will enable longitudinal studies to better understand disease progression and enable the identification and treatment of PD patients at the earliest possible time, significantly increasing the chances of therapies improving the quality of patients’ lives. Further, therapies that slow PD disease progression will benefit significantly from having a clinical biomarker to monitor target engagement and disease progression to guide their development and de-risk clinical trials.
Next Steps for Development: The outcome of this grant is a robust and validated Miro1 biomarker assay using white blood cells. Upon development of the Miro1 biomarker assay, the assay will begin GLP-clinical assay validation for future use in longitudinal studies and clinical trials.