Study Rationale: There is an urgent need to develop non-invasive biomarkers that are able to diagnose and track the progression of Parkinson’s disease (PD). Focused ultrasound blood brain barrier opening (FUS-BBBO) is a safe tool that allows the recovery of molecules from brain regions where this technology is applied. We propose to use FUS-BBBO to recover brain proteins from targeted brain regions in a mouse model of PD. By identifying and tracking changes on protein deposition within key brain regions over time, this method has the potential to become a valuable translational tool to diagnose and monitor the progression of PD.
Hypothesis: We hypothesize that FUS-BBBO will facilitate the transport of alpha-synuclein and other abnormally expressed proteins from the targeted brain regions into the peripheral blood. We also hypothesize that this approach will allow us to identify and monitor changes in the amount of proteins deposited in different areas of the brain.
Study Design: In this study we will use safe levels of ultrasound that is focused through an intact skull on specific brain regions to open very small pores between the cells of blood vessels. These pores are too small to cause trouble and in fact close up on their own within hours. However, before they close, some of the proteins present between brain cells of Parkinson’s disease-affected animals will leak into the blood where these brain-derived proteins can be studied, used to diagnose the disease, or inform how the disease progresses or responds to therapy.
Impact on Diagnosis/Treatment of Parkinson’s disease: If we are successful, this study will develop a new and innovative tool to identify changes that occur in particular areas of the brain and to monitor them over time. Since FUS-BBBO has already been safely used in humans, the findings of this study are likely to help develop a safe and noninvasive clinical tool.
Next Steps for Development: An FDA-approved FUS system has been acquired by BCM and we have initiated collaborative discussions with the manufacturers to use the system for the development of PD biomarkers in humans. BCM has one of the largest PD clinical and research centers in the US. If successful, we are uniquely positioned to translate this approach into a PD cohort.