RecruitingPhase 1NCT06687837

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

Phase I Trial of Autologous Induced Pluripotent Stem Cell-derived Dopaminergic Progenitor Cell Transplantation for Parkinson's Disease

Sponsor

Jeffrey S. Schweitzer, MD, PhD

Enrollment

8 participants

Start Date

Apr 29, 2025

Study Type

INTERVENTIONAL

Conditions

Parkinson Disease

Summary

The goal of this clinical trial is to assess the safety and tolerability of the surgical transplantation of dopaminergic progenitor cells into the brains of participants with Parkinson's disease. The transplanted dopaminergic cells will be derived from the participant's own skin cells.

Eligibility

Min Age: 45 YearsMax Age: 80 Years

Inclusion Criteria18

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 Criteria24

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

Interventions

BIOLOGICALautologous dopaminergic cell implantation

Dopaminergic progenitor cells derived from autologous induced pluripotent stem cells will be injected into the brain in two cohorts of Parkinson's patients, one receiving low dose and the other high dose (4 and 8 million cells, respectively)