Study Rationale: There is a great unmet clinical need for more effective therapies to treat Parkinson Disease (PD). Successful clinical translation of new disease-modifying treatments can be accelerated by imaging methods that can specifically probe the molecular mechanisms of PD disease. In particular, the brain neurochemistry is markedly altered in PD due to neuroinflammation and mitochondrial dysfunction. Our project will develop new molecular MRI imaging methods using the characteristic spectroscopic signatures of brain metabolites impacted by neuroinflammation and mitochondrial dysfunction, which can be used to objectively assess treatment response in PD patients.
Hypothesis:
Our hypothesis is that molecular alterations specific to clinical stages of PD disease can be imaged non-invasively by metabolic MR spectroscopic imaging to track disease progression and treatment response.
Study Design:
Our study has two aims: 1) in the first 6 months we will develop a novel molecular imaging method that is able to image with high sensitivity, specificity and resolution an extended neurochemical profile of 12 metabolites that are biomarkers of neuronal health, neuroinflammation and energy metabolism, 2) in the next 18 months we will perform a cross-sectional study to validate in PD patients the performance of the imaging method to distinguish between prodromal (15 patients), early-stage (15 patients) and late-stage (15 patients) clinical symptoms.
Impact on Diagnosis/Treatment of Parkinson’s disease:
The new metabolic imaging method will enable non-invasive diagnosis of disease stages in PD patients linked to specific molecular mechanisms of disease. Current imaging methods lack in specificity for molecular mechanisms, hence there is a disconnect between non-invasive imaging and clinical symptoms.
Next Steps for Development:
The new metabolic imaging method can be used to track disease course and hence can be employed in clinical trials to objectively measure response to disease-modifying treatments. In the next steps we will perform: 1) a longitudinal imaging study along the natural history of disease to establish and validate the performance of imaging to measure a change in molecular biomarkers in the same PD patient over time; 2) employ this methodology in clinical trials of new treatments in PD patients.