Dopamine Neuron Transplantation for Parkinson's Disease

Overseen By Penelope Hallett, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Penelope J. Hallett, Ph.D.

Must be taking: Dopamine drugs

Must not be taking: Anticoagulants, Investigational drugs

Disqualifiers: Intracranial surgeries, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Baseline to 12 months post-transplant

6 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot be on chronic anticoagulation medication (blood thinners) and should not have poorly controlled blood pressure or diabetes. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Autologous iPSC-Derived Dopamine Neuron Transplantation for Parkinson's Disease?

Research shows that transplanting dopamine neurons derived from a patient's own cells can lead to motor improvements in animal models of Parkinson's disease, with successful neuron survival and growth. Additionally, a pioneering study demonstrated the feasibility of this approach in a human patient, suggesting potential for effective treatment. ^{1 2 3 4 5}

Is dopamine neuron transplantation for Parkinson's disease safe in humans?

Preclinical studies in animals, including mice and primates, show that dopamine neuron transplantation using induced pluripotent stem cells (iPSCs) does not cause tumors or toxicity and is considered safe. These studies support the potential for safe use in humans, although long-term human data is still needed. ^{1 2 6 7 8}

How is the treatment of autologous iPSC-derived dopamine neuron transplantation unique for Parkinson's disease?

This treatment is unique because it uses the patient's own cells, transformed into dopamine-producing neurons, to replace the lost neurons in Parkinson's disease, potentially reducing the need for immunosuppressive drugs and offering a personalized approach to therapy. ^{1 2 5 9 10}

Eligibility Criteria

This trial is for individuals with Parkinson's Disease who are eligible to undergo a surgical procedure where investigational cells will be injected into their brain. Specific eligibility criteria details were not provided.

Inclusion Criteria

No gross abnormalities on MRI, including hydrocephalus or extensive white matter disease

I have been diagnosed with Parkinson's disease for 5 years or more.

No significant untreated depression (Beck Depression Inventory 2)

Exclusion Criteria

My condition is a type of Parkinsonism that is not typical Parkinson's disease.

Inability to have an MRI

Life expectancy < 6 months due to concomitant illnesses

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous iPSC-derived dopamine neuron transplantation into the putamen

Baseline to 12 months post-transplant

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and changes in Parkinson's disease symptoms

18 months following transplantation

Treatment Details

Interventions

• Autologous iPSC-Derived Dopamine Neuron Transplantation

Trial Overview The study is testing the safety of transplanting dopamine neurons derived from a patient's own induced pluripotent stem cells (iPSCs) into their brain, as a potential treatment for Parkinson's Disease.

Participant Groups

Group I: Autologous midbrain dopamine neurons Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Penelope J. Hallett, Ph.D.

Lead Sponsor

Trials

1

Recruited

6+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Oryon Cell Therapies

Collaborator

Trials

1

Recruited

6+

Findings from Research

A groundbreaking study demonstrated the successful transplantation of dopamine neurons derived from a patient's own skin cells into a patient with Parkinson's disease, highlighting the potential for personalized cell therapy.

This approach shows promise for autologous transplantation, meaning the patient's own cells are used, which may reduce the risk of rejection and improve treatment outcomes for dopamine cell replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From Skin to Brain: A Parkinson's Disease Patient Transplanted with His Own Cells. Parmar, M., Björklund, A.[2021]

Dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line were found to be safe, showing no tumorigenicity or toxicity in pre-clinical studies with immunodeficient mice.

Transplanting these DAPs into the striatum of rats with induced Parkinson's disease led to significant behavioral improvements, supporting their potential efficacy as a treatment for Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson's disease. Doi, D., Magotani, H., Kikuchi, T., et al.[2022]

Stem cell therapy for Parkinson's disease aims to restore dopamine production and improve synapse formation, with fetal ventral-midbrain cells showing promise in alleviating symptoms.

Induced pluripotent stem cells (iPSCs) can be effectively used to generate dopaminergic neurons for transplantation, providing a safe and efficient alternative donor cell source for treating Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

iPS cell therapy for Parkinson's disease. Takahashi, J.[2017]

Transplanting dopaminergic neurons derived from human pluripotent stem cells shows potential as a treatment for Parkinson's disease.

Recent studies have identified specific markers for midbrain dopaminergic progenitors, which can enhance the process of deriving these neurons and help predict the amount of dopamine-producing neurons after they are transplanted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seq-ing Markers of Midbrain Dopamine Neurons. Osborn, T., Hallett, PJ.[2021]

The study demonstrated that autologous induced pluripotent stem cell (iPSC)-derived dopamine neurons can improve behavior in a cynomolgus monkey model of Parkinson's disease, indicating potential efficacy for treating the condition.

No immunosuppression was needed for the grafts, and histological analysis showed a significant number of surviving dopamine neurons without any overgrowth, suggesting a safe approach for cell replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous iPSC-derived dopamine neuron transplantation in a nonhuman primate Parkinson's disease model. Wang, S., Zou, C., Fu, L., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of patient-derived cells shows promise for Parkinson's disease. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Neurite Outgrowth and Gene Expression Profile Correlate with Efficacy of Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Stem cells and Parkinson's disease: toward a treatment, not a cure. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

From Skin to Brain: A Parkinson's Disease Patient Transplanted with His Own Cells. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson's disease. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

iPS cell therapy for Parkinson's disease. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Seq-ing Markers of Midbrain Dopamine Neurons. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Autologous iPSC-derived dopamine neuron transplantation in a nonhuman primate Parkinson's disease model. [2020]