Clinical trial NCT06422208: Autologous iPSC-Derived Dopamine Neuron Transplantation for Parkinson's Disease
Official title: A Phase 1 Clinical Trial of Autologous iPSC-Derived Dopamine Neuron Transplantation for Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Oryon Cell Therapies
First posted: 2024-05-20
Enrollment: 6
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is evaluating an investigational cell product called autologous induced pluripotent stem cell (iPSC)-derived dopamine neurons. This research study is a single-center Phase 1 clinical trial, which will test the safety of injecting the investigational cell product into the brain of subjects with Parkinson's disease.

Detailed description: The goal of this research study is to test a new treatment for Parkinson's disease. Parkinson's disease is a progressive disease that causes people to lose specific brain cells called midbrain dopamine neurons. When these dopamine neurons are lost, it leads to a lack of dopamine in the brain. When there is not enough dopamine, people with Parkinson's disease experience problems with their movement. This trial will test whether new dopamine neurons made from blood cells from subjects with Parkinson's disease are safe when surgically injected into the area of the brain affected (called the putamen) of the same subjects (called autologous transplantation). The trial will assess the safety of the injected cells and will also measure the effects of the transplanted autologous dopamine neurons on Parkinson's disease symptoms.

Eligibility criteria: Inclusion Criteria:

* Males and females between ages 55 to eighty.
* Diagnosis of Parkinson's disease with motor symptoms by neurologist according to Movement Disorder Society (MDS) 2015 Clinical Diagnostic Criteria for Parkinson's disease.
* Diagnosis of Parkinson's disease for at least 5 years.
* Dopamine drug responsiveness demonstrated by a positive "on/off" test with at least a 30% improvement on UPDRS III (motor) scale.
* No gross abnormalities on MRI, including hydrocephalus or extensive white matter disease.
* No significant cognitive impairment (Montreal Cognitive Assessment).
* No significant untreated depression (Beck Depression Inventory 2).
* Up to date cancer screening per primary MD.
* Able to understand trial requirements and intervention procedures and provide written informed consent.

Exclusion Criteria:

* History of intracranial surgeries.
* Any previous thalamotomy, pallidotomy or deep brain stimulation.
* Atypical Parkinsonism (Parkinsonism-Plus syndrome, secondary parkinsonism, hereditary parkinsonism)
* History of psychiatric disorders including schizophrenia or psychosis likely to compromise with ability to comply with trial protocol requirements.
* Prior history of intracerebral, subdural, or epidural hemorrhage.
* History of malignancy within 5 years.
* Inability to have an MRI.
* Life expectancy \< 6 months due to concomitant illnesses.
* Ingestion of investigational drug or recipient of investigational procedure within 6 months prior to trial.
* Subjects with active cardiovascular and cerebrovascular disease within 6 months prior to signing the informed consent form:

  1. 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
  2. Severe arrhythmia
  3. History of cardiovascular surgery (cardiac, vascular stent surgery, angioplasty);
  4. History of stroke or transient ischemic attack
  5. History of subarachnoid hemorrhage
  6. Subjects with major vascular diseases (aortic aneurysm, aortic dissecting aneurysm, internal carotid artery stenosis)
* Hypertensive subjects with poorly controlled blood pressure (defined as blood pressure above 160/100 mmHg despite treatment with antihypertensive drugs) and subjects with severe postural hypotension.
* Abnormal pre-operative coagulation labs.
* Any necessary chronic anticoagulation medication in use (not including antiplatelet therapy and chronic NSAID).
* Diabetic subjects with poorly controlled blood glucose (glycosylated hemoglobin \> 9.0%, or fasting plasma glucose (FPG) ≥ 11.1 mmol/L).
* Active infectious disease. Subjects known to have tested positive for HIV, Human T-lymphotropic Virus, Hepatitis B Virus, Hepatitis C Virus, Cytomegalovirus (IgM \> IgG) and/or syphilis will be evaluated by an expert as to subject eligibility based on the subject's infectious status.
* Any illness which, in the Investigator's judgment, will interfere with the subject's ability to comply with the protocol, compromise subject safety, or interfere with the interpretation of the trial results.
* Active clinical infection being treated by antibiotics within one week of enrollment.
* Known drug or alcohol dependence or any other clinical factors or conditions (for example, history of seizures) which will interfere with the trial conduct or interpretation of the results or who in the opinion of the investigator are not suitable to participate.
* Unwilling and/or not able to give written informed consent.

Primary outcomes:
measure: Safety: number and severity of adverse events and serious adverse events
timeFrame: Baseline to 12 months post-transplant and baseline to 18 months post-transplant
Secondary outcomes:
measure: Change in UPDRS Part III
timeFrame: 18 months following transplantation
measure: Change in ON time without troublesome dyskinesia
timeFrame: 18 months following transplantation
measure: Change in OFF time
timeFrame: 18 months following transplantation
measure: Change in baseline Levodopa Equivalent Daily Dose
timeFrame: 18 months following transplantation
measure: Change in Unified Dyskinesia Rating Scale
timeFrame: 18 months following transplantation
measure: Change in UPDRS Part II
timeFrame: 18 months following transplantation
measure: Change in MoCA
timeFrame: 18 months following transplantation
measure: Change in DaTscan
timeFrame: Baseline to 18 months following transplantation
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
Study officials:
References:
citation: Osborn TM, Hallett PJ, Schumacher JM, Isacson O. Advantages and Recent Developments of Autologous Cell Therapy for Parkinson's Disease Patients. Front Cell Neurosci. 2020 Apr 3;14:58. doi: 10.3389/fncel.2020.00058. eCollection 2020.
citation: Hallett PJ, Deleidi M, Astradsson A, Smith GA, Cooper O, Osborn TM, Sundberg M, Moore MA, Perez-Torres E, Brownell AL, Schumacher JM, Spealman RD, Isacson O. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease. Cell Stem Cell. 2015 Mar 5;16(3):269-74. doi: 10.1016/j.stem.2015.01.018. Epub 2015 Feb 26.
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citation: Mendez I, Sanchez-Pernaute R, Cooper O, Vinuela A, Ferrari D, Bjorklund L, Dagher A, Isacson O. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease. Brain. 2005 Jul;128(Pt 7):1498-510. doi: 10.1093/brain/awh510. Epub 2005 May 4.
citation: Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5856-61. doi: 10.1073/pnas.0801677105. Epub 2008 Apr 7.
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