Autologous iPSC-Derived Dopamine Neuron Transplantation for Parkinson's Disease

NCT06422208 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 2 other identifiers: 2023P003609U01NS109463
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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 1/2a clinical trial, which will test the safety of injecting the investigational cell product into the brain of subjects with Parkinson's disease.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Safety: number and severity of adverse events and serious adverse events

  To assess the safety of autologous transplantation of cryopreserved midbrain dopamine neurons into the putamen of subjects with Parkinson's disease by measuring (1) the incidence of serious adverse events at 12 months and 18 months post-transplantation and (2) the incidence and severity of all intervention emergent adverse events.

  Baseline to 12 months post-transplant and baseline to 18 months post-transplant

Secondary Outcomes (8)

• Change in UPDRS Part III

  18 months following transplantation

• Change in ON time without troublesome dyskinesia

  18 months following transplantation

• Change in OFF time

  18 months following transplantation

• Change in baseline Levodopa Equivalent Daily Dose

  18 months following transplantation

• Change in Unified Dyskinesia Rating Scale

  18 months following transplantation

Study Arms (1)

Autologous midbrain dopamine neurons

EXPERIMENTAL

Biological: Autologous midbrain dopamine neurons

Interventions

Autologous midbrain dopamine neurons BIOLOGICAL

The autologous midbrain dopamine neurons are a experimental cryopreserved cell product derived from human autologous induced pluripotent stem cells. The autologous midbrain dopamine neurons will be surgically administered into the putamen, unilaterally, in a single surgical session.

Autologous midbrain dopamine neurons

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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);
• History of stroke or transient ischemic attack
• History of subarachnoid hemorrhage

Sponsors & Collaborators

• Penelope J. Hallett, Ph.D.: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Oryon Cell Therapies: collaborator

Study Sites (1)

Brigham & Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Related Publications (12)

• 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.

  PMID: 32317934 BACKGROUND

• 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.

  PMID: 25732245 BACKGROUND

• Hallett PJ, Cooper O, Sadi D, Robertson H, Mendez I, Isacson O. Long-term health of dopaminergic neuron transplants in Parkinson's disease patients. Cell Rep. 2014 Jun 26;7(6):1755-61. doi: 10.1016/j.celrep.2014.05.027. Epub 2014 Jun 6.

  PMID: 24910427 BACKGROUND

• Cooper O, Hallett P, Isacson O. Using stem cells and iPS cells to discover new treatments for Parkinson's disease. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1(0 1):S14-6. doi: 10.1016/S1353-8020(11)70007-4.

  PMID: 22166414 BACKGROUND

• Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, Yow A, Soldner F, Hockemeyer D, Hallett PJ, Osborn T, Jaenisch R, Isacson O. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15921-6. doi: 10.1073/pnas.1010209107. Epub 2010 Aug 23.

  PMID: 20798034 BACKGROUND

• Cooper O, Astradsson A, Hallett P, Robertson H, Mendez I, Isacson O. Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients. J Neurol. 2009 Aug;256 Suppl 3:310-6. doi: 10.1007/s00415-009-5242-z.

  PMID: 19711122 BACKGROUND

• Mendez I, Vinuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski JQ, Isacson O. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat Med. 2008 May;14(5):507-9. doi: 10.1038/nm1752. Epub 2008 Apr 6.

  PMID: 18391961 BACKGROUND

• Fink JS, Schumacher JM, Ellias SL, Palmer EP, Saint-Hilaire M, Shannon K, Penn R, Starr P, VanHorne C, Kott HS, Dempsey PK, Fischman AJ, Raineri R, Manhart C, Dinsmore J, Isacson O. Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results. Cell Transplant. 2000 Mar-Apr;9(2):273-8. doi: 10.1177/096368970000900212.

  PMID: 10811399 BACKGROUND

• Schumacher JM, Ellias SA, Palmer EP, Kott HS, Dinsmore J, Dempsey PK, Fischman AJ, Thomas C, Feldman RG, Kassissieh S, Raineri R, Manhart C, Penney D, Fink JS, Isacson O. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology. 2000 Mar 14;54(5):1042-50. doi: 10.1212/wnl.54.5.1042.

  PMID: 10720272 BACKGROUND

• 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.

  PMID: 15872020 BACKGROUND

• 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.

  PMID: 18391196 BACKGROUND

• Cooper O, Hargus G, Deleidi M, Blak A, Osborn T, Marlow E, Lee K, Levy A, Perez-Torres E, Yow A, Isacson O. Differentiation of human ES and Parkinson's disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid. Mol Cell Neurosci. 2010 Nov;45(3):258-66. doi: 10.1016/j.mcn.2010.06.017. Epub 2010 Jul 24.

  PMID: 20603216 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: May 20, 2024
• Study Start: August 7, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)