Stem Cell Transplantation for Parkinson's Disease

Overseen By Jeffrey S Schweitzer, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jeffrey S. Schweitzer, MD, PhD

Must be taking: Levodopa, Dopamine agonists

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Dementia, Psychosis, Stroke, Cancer, others

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

Compensation: Varies

Number of Visits: 3

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you have a stable regimen of Parkinson's medications, like levodopa and dopamine agonists, for at least 4 weeks before screening. However, if you are taking anticoagulation or antiplatelet agents, you must stop them one week before and two days after surgery.

Is stem cell transplantation for Parkinson's disease safe for humans?

Research on stem cell transplantation for Parkinson's disease, including studies on animals and a pioneering human case, suggests it can be safe. In a monkey model, no harmful overgrowth of transplanted cells was observed, and a human patient successfully received a transplant of dopamine neurons derived from their own cells, indicating potential safety. ^{1 2 3 4 5}

How is the treatment Autologous Dopaminergic Cell Implantation different from other treatments for Parkinson's disease?

This treatment is unique because it uses the patient's own stem cells to create dopaminergic neurons, which are then implanted to help restore dopamine levels in the brain, potentially reducing symptoms of Parkinson's disease. Unlike traditional treatments that mainly manage symptoms, this approach aims to repair the underlying neuronal pathways. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment Autologous Dopaminergic Cell Implantation for Parkinson's Disease?

Research shows that using a patient's own cells to create dopamine-producing neurons is feasible and has been tested in a patient with Parkinson's disease, demonstrating the potential for this treatment to replace lost dopamine cells. Additionally, past studies have shown encouraging results with dopamine cell transplants in patients, indicating that this approach could help manage Parkinson's symptoms. ^{1 5 9 10 11}

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease who experience symptoms like tremors and stiffness. Participants will have their own skin cells used to create special nerve cells that are missing in this disease.

Inclusion Criteria

English proficiency sufficient to understand the consent form and participate in a discussion of risks and benefits

I have been diagnosed with Parkinson's Disease.

My Parkinson's is advanced, affecting my movement without medication.

Exclusion Criteria

Pregnant or nursing women

I have had a stroke or a transient ischemic attack.

Subjects with alcohol or drug addiction

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Production

Fibroblast samples are collected from participants to produce autologous midbrain dopaminergic progenitor cells

4-8 weeks

Transplantation

Surgical transplantation of dopaminergic progenitor cells into the putamen under general anesthesia

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness through clinical assessments and neuroimaging

2 years

Regular visits (in-person and virtual) over 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Dopaminergic Cell Implantation

Trial Overview The study tests a new procedure where doctors take a person's skin cells, turn them into nerve cells that produce dopamine (which are lacking in Parkinson's), and then put these back into the patient’s brain.

How Is the Trial Designed?

Group I: Low dose administration Experimental Treatment 1 Intervention

4 million autologous dopaminergic cells will be implanted into the putamen on each side of the brain

Group II: High dose administration Experimental Treatment 1 Intervention

8 million autologous dopaminergic cells will be implanted into the putamen on each side of the brain

Who Is Running the Clinical Trial?

Jeffrey S. Schweitzer, MD, PhD

Lead Sponsor

Trials

1

Recruited

8+

Published Research Related to This Trial

Stem-cell-derived transplants are being developed as a potential treatment for Parkinson's disease, with a focus on creating a clinical-grade dopaminergic progenitor cell product.

The study emphasizes the importance of rigorous testing to ensure the safety and efficacy of these stem-cell-derived products before they enter clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Embryonic stem cells go from bench to bedside for Parkinson's disease. Parish, CL., Thompson, LH.[2022]

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]

Over three decades of research into dopamine cell replacement therapy for Parkinson's disease has led to the transplantation of fetal-derived dopamine neuroblasts in 18 patients, with some encouraging results regarding neuron survival and function in the human brain.

The journey has included both significant breakthroughs and setbacks, highlighting the complexity of developing effective treatments for Parkinson's disease and the ongoing advancements in this field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacing Dopamine Neurons in Parkinson's Disease: How did it happen? Björklund, A., Lindvall, O.[2023]

Stem cell-derived dopamine neuron transplantation shows promise as a potential curative therapy for Parkinson's disease, addressing the loss of dopaminergic neurons and aiming to restore dopamine levels in the brain.

Factors such as the source and quality of stem cells, patient age, disease progression stage, surgical techniques, and immunosuppression practices significantly influence the outcomes of cell transplantation, highlighting the need for careful consideration in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status of Stem Cell-Derived Therapies for Parkinson's Disease: From Cell Assessment and Imaging Modalities to Clinical Trials. Jang, SE., Qiu, L., Chan, LL., et al.[2020]

Neurotransplantation for treating Parkinson's disease has been in human trials for over 15 years but faces significant political and scientific challenges that hinder progress.

Recent advancements include the transplantation of new dopaminergic cell lines into a primate model of Parkinson's disease, marking a crucial step in developing stem cell therapies for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise of stem cells in Parkinson disease. Langston, JW.[2018]

In a study using rat models of Parkinson's disease, L-DOPA treatment did not negatively affect the survival or function of human embryonic stem cell-derived dopaminergic neuron grafts, suggesting it is safe to use alongside grafting procedures.

L-DOPA administration led to early improvements in dyskinesia, indicating that the grafts may help manage dopamine levels sooner than expected, which is important for optimizing patient outcomes in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Embryonic Stem Cell-Derived Dopaminergic Grafts Alleviate L-DOPA Induced Dyskinesia. Elabi, OF., Pass, R., Sormonta, I., et al.[2022]

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]

Autologous adult neural stem cells (NSCs) present a promising cell therapy option for treating Parkinson's disease by potentially replacing lost dopaminergic neurons, addressing the core issue of dopamine depletion in the striatum.

Using NSCs from adult tissue avoids ethical concerns associated with fetal or embryonic stem cells and allows for personalized treatment through autologous transplantation, where the patient's own cells are used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous neural stem cell transplantation: a new treatment option for Parkinson's disease? Arias-Carrión, O., Yuan, TF.[2009]

Stem cell therapy for Parkinson's disease aims to repair damaged neuronal pathways by using either the patient's own neural stem cells or grafted dopaminergic neurons, which can help restore dopamine levels and improve symptoms.

While embryonic stem cells show promise due to their ability to proliferate and differentiate, concerns about tumor formation and ethical issues pose significant challenges for their use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell therapy for Parkinson's disease. Takahashi, J.[2007]

Stem cells can potentially be used to treat Parkinson's disease by generating new dopaminergic neurons through cell replacement therapy, which involves using embryonic stem cells, multipotent stem cells, or neuronal progenitor cells.

Another promising approach is engineering multipotent stem cells to produce glial cell-line derived neurotrophic factor, which supports the survival and growth of dopaminergic neurons, offering a neuroprotective and neuroregenerative strategy for treating the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cells in the treatment of Parkinson's disease. Arenas, E.[2019]

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]

Citations

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

Embryonic stem cells go from bench to bedside for Parkinson's disease. [2022]

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

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

Replacing Dopamine Neurons in Parkinson's Disease: How did it happen? [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Current Status of Stem Cell-Derived Therapies for Parkinson's Disease: From Cell Assessment and Imaging Modalities to Clinical Trials. [2020]

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

The promise of stem cells in Parkinson disease. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Human Embryonic Stem Cell-Derived Dopaminergic Grafts Alleviate L-DOPA Induced Dyskinesia. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Autologous neural stem cell transplantation: a new treatment option for Parkinson's disease? [2009]

9. England pubmed.ncbi.nlm.nih.gov

Stem cell therapy for Parkinson's disease. [2007]

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

Stem cells in the treatment of Parkinson's disease. [2019]

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

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