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 2015Parkinson's diagnostic criteria.

• Age 45 - 80 years

• English proficiency sufficient to understand the consent form and participate in adiscussion 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 atleast 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:

1. Platelets > 100×109/L (transfusion independent)

2. Prothrombin time / partial thromboplastin time in normal range andinternational normalized ratio ≤ 1.3

3. Aspartate aminotransferase and alanine aminotransferase < 2.5x the upper limitof normal

4. Serum creatinine ≤ 1.5mg/dL

5. White blood cell count < 12×109/L.

6. Estimated glomerular filtration rate ≥ 30 mL/min/1.73m2

• Subject agrees to defer elective neurological surgery, including deep brainstimulation or lesional procedure for PD, invasive treatments, including levodopa orapomorphine infusion, or pump- pump-administered levodopa intestinal gel, untilafter the study's primary outcome is completed.

• Findings on baseline 18F-DOPA PET imaging consistent with dopaminergic denervationof the putamen

• Subject is willing and able to comply with all study visits and procedures in theopinion 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 knowngenetic mutation predisposing to the development of Parkinson's disease (i.e. thisinitial study is confined to the more common "sporadic" vs a "genetic" form of thedisease).

• Atypical Parkinsonism (Parkinson's-Plus syndrome, secondary parkinsonism)

• Moderate or severe levodopa-induced dyskinesias in any body segment (such patientswere found to be more prone to graft-induced dyskinesias in the fetal tissue studiesthat are proof of priniciple for this therapy)

• Neurologic history or imaging demonstrating brain pathology not directly related toParkinson's disease that is likely to interfere with study compliance or assessmentof 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 inthe past 5 years.

• History of intracranial surgery including deep brain stimulation, focusedultrasound, stereotactic or radiosurgical lesion therapy

• History of malignancy within 5 years. Exceptions will be made for treated cutaneoussquamous cell or basal cell carcinoma without evidence of metastasis.

• Use of anticoagulation / antiplatelet agents that cannot be stopped for one week inadvance 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 monthsprior to signing the informed consent form.

• History of severe heart failure (congestive heart failure of New York HeartAssociation Class II or above or left ventricular ejection fraction < 35% by anyexamination 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 bloodpressure consistently above 160/100 mmHg despite treatment with antihypertensivedrugs) 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