Treating Parkinson's Disease Through Transplantation of Autologous Stem Cell-Derived Dopaminergic Neurons

Inclusion criteria

• Diagnosis of Parkinson's Disease consistent with the Movement Disorders Society 2015 Parkinson's diagnostic criteria.
• Age 45 - 80 years
• English proficiency sufficient to understand the consent form and participate in a discussion of risks and benefits
• At least 5 years since Parkinson's disease motor symptom onset
• Modified Hoehn and Yahr stage 3-4 in "off"-medication state
• Motor symptoms responsive to levodopa and/or dopamine agonist, defined as taking at least 300 mg/day of levodopa and exhibiting improvement between "off" and "on" MDS-UPDRS of at least 30%
• At least 3 hours of cumulative "off" time per day
• Stable regimen of Parkinson's medications, including levodopa and dopamine agonists, for at least 4 weeks prior to screening.
• Acceptable surgical laboratory values including:
• Platelets \> 100×109/L (transfusion independent)
• Prothrombin time / partial thromboplastin time in normal range and international normalized ratio ≤ 1.3
• Aspartate aminotransferase and alanine aminotransferase \< 2.5x the upper limit of normal
• Serum creatinine ≤ 1.5mg/dL
• White blood cell count \< 12×109/L.
• Estimated glomerular filtration rate ≥ 30 mL/min/1.73m2
• Subject agrees to defer elective neurological surgery, including deep brain stimulation or lesional procedure for PD, invasive treatments, including levodopa or apomorphine infusion, or pump- pump-administered levodopa intestinal gel, until after the study's primary outcome is completed.
• Findings on baseline 18F-DOPA PET imaging consistent with dopaminergic denervation of the putamen
• Subject is willing and able to comply with all study visits and procedures in the opinion of the Investigator.

Exclusion criteria

• Subjects unable to give consent due to dementia or psychosis.
• Montreal Cognitive Assessment (MoCA) score \< 26
• Subjects with a first-degree relative with Parkinson's disease or with a known genetic mutation predisposing to the development of Parkinson's disease (i.e. this initial study is confined to the more common "sporadic" vs a "genetic" form of the disease).
• Atypical Parkinsonism (Parkinson's-Plus syndrome, secondary parkinsonism)
• Moderate or severe levodopa-induced dyskinesias in any body segment (such patients were found to be more prone to graft-induced dyskinesias in the fetal tissue studies that are proof of priniciple for this therapy)
• Neurologic history or imaging demonstrating brain pathology not directly related to Parkinson's disease that is likely to interfere with study compliance or assessment of Parkinson's related motor disability.
• History of stroke or transient ischemic attack
• History of subarachnoid hemorrhage
• Presence or history of psychosis within 12 months of screening
• Suicidal ideation associated with intent or plan in the past 12 months (an answer of "yes" to C-SSRS questions 4 or 5) or with a previous history of suicide attempts in the past 5 years.
• History of intracranial surgery including deep brain stimulation, focused ultrasound, stereotactic or radiosurgical lesion therapy
• History of malignancy within 5 years. Exceptions will be made for treated cutaneous squamous cell or basal cell carcinoma without evidence of metastasis.
• Use of anticoagulation / antiplatelet agents that cannot be stopped for one week in advance of and two days following surgery without significant risk to the subject
• Use of chronic immunosuppressive therapy including chronic steroids
• Contraindication to MRI or MRI contrast agents
• Pregnant or nursing women
• Subjects with active cardiovascular and cerebrovascular disease within 6 months prior to signing the informed consent form.
• History of severe heart failure (congestive heart failure of New York Heart Association Class II or above or left ventricular ejection fraction \< 35% by any examination method), unstable angina pectoris and myocardial infarction/
• Severe arrhythmia
• History of cardiovascular surgery (cardiac, vascular stent surgery, angioplasty)
• Patients with major vascular diseases (aortic aneurysm, aortic dissecting aneurysm, internal carotid artery stenosis)
• Hypertensive patients with poorly controlled blood pressure (defined as blood pressure consistently above 160/100 mmHg despite treatment with antihypertensive drugs) and patients with severe postural hypotension
• Diabetic patients with poorly controlled blood glucose (glycosylated hemoglobin \> 9.0%, or fasting plasma glucose (FPG) ≥ 11.1 mmol/L);
• Subjects with alcohol or drug addiction