The goal of this study is to establish safety and feasibility of intracerebral delivery of GCase via MRgFUS. This technique may offer potential benefits given the exposure of the putamen to GCase in animal models has been shown to be efficacious in improving Parkinson's disease pathology and phenotype.

This is a two-arm, open-label, intervention only phase I/II clinical study. One arm of the study will enroll seven (7) GBA PD patients and the other arm seven (7) idiopathic PD patients. During the intervention phase, the first four subjects of each arm will receive three transcranial bilateral putamenal GCase at 30 IU/kg IV every two weeks, followed by 60 IU/kg in the next three subjects. Following three treatments in this study, the subjects will be followed for twelve months.

Inclusion Criteria:

• Men or women between age 35 and 80 years, inclusive.
• Able and willing to give informed consent.
• Diagnosis of PD satisfying MDS Clinical Diagnostic Criteria for PD
• At least 2 years from initial diagnosis
• Hoehn and Yahr Stage 1-3 on PD medication
• Dopaminergic deficit by a positive DAT SPECT scan
• On stable regimen of PD medications for at least 90 days prior to the study
• American Society of Anesthesiologists (ASA) score 1-3
• Harbor at least one GBA mutation if enrolled in the GBA PD arm or two wild-type GBA alleles if enrolled in the idiopathic PD arm

Exclusion Criteria:

• Positive pregnancy test (for pre-menopausal women).
• Contraindication to DEFINITY ultrasound contrast agent or perflutren (e.g. hypersensitivity, known left or bidirectional cardiac shunt)
• Contraindication to MRI or gadolinium-DTPA (e.g. incompatible device, hypersensitivity)
• Insulin-dependent diabetes mellitus that is not well-controlled or that in the Investigator's opinion precludes participation in the study.
• Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis.
• Currently participating in another clinical therapeutic trial
• Patient receiving bevacizumab (Avastin) therapy
• Subjects with evidence of cranial or systemic infection.
• Cerebral or systemic vasculopathy.
• Documented cerebral infarction within the past 12 months or TIA in the past 1 month.
• Contraindication to GCase enzyme therapy, specifically previous hypersensitivity reaction to GCase enzyme therapy
• Parkinsonism plus symptoms, secondary parkinsonism
• Previous neurosurgical procedure for PD