MR-guided Focused Ultrasound Plus GCase

This trial is testing a combination approach for Parkinson's disease: using focused ultrasound (a non-surgical technique that uses sound waves to temporarily open the blood-brain barrier) to deliver an enzyme called GCase directly into the brain. GCase deficiency is linked to a subset of Parkinson's cases and may contribute to the disease process. **You may be eligible if...** - You are between 35 and 80 years old - You have been diagnosed with Parkinson's disease for at least 2 years - Your Parkinson's is at Hoehn and Yahr stage 1–3 (mild to moderate) while on medication - You carry a GBA gene mutation (for the GBA arm) OR have no GBA mutation (for the idiopathic arm) - A special brain scan (DAT SPECT) confirms dopamine deficiency - Your Parkinson's medications have been stable for at least 90 days **You may NOT be eligible if...** - You are a pre-menopausal woman with a positive pregnancy test - You have a metal implant or other contraindication to MRI or ultrasound contrast agents - You have severe kidney problems (eGFR under 30) or are on dialysis - You have poorly controlled diabetes - You have had a stroke in the past year, or a TIA in the past month - You have had prior brain surgery for Parkinson's - You have 'Parkinson's plus' (atypical parkinsonism) Talk to your doctor to see if this trial is right for you.