Mesenchymal Stem Cell Therapy for Multiple System Atrophy

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must not be taking: Neuroleptics, Anticholinergics, others

Disqualifiers: Cancer, Dementia, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that certain medications affecting autonomic function be stopped 48 hours before testing. If you're taking midodrine, anticholinergic, alpha and beta adrenergic antagonists, or similar medications, you will need to pause them temporarily. Fludrocortisone up to 0.2 mg per day is allowed.

What data supports the effectiveness of the treatment for Multiple System Atrophy?

Research shows that mesenchymal stem cell therapy can delay the progression of neurological deficits in patients with Multiple System Atrophy, leading to functional improvements. In a study, patients treated with these stem cells showed better outcomes on a rating scale for the disease compared to those who did not receive the treatment. ^{1 2 3 4 5}

Is mesenchymal stem cell therapy safe for humans?

Research shows that mesenchymal stem cell therapy, including autologous adipose-derived stem cells, is generally safe in humans, with no serious adverse events reported in studies for various conditions. ^{1 2 6 7 8}

How is autologous mesenchymal stem cell therapy different from other treatments for multiple system atrophy?

Autologous mesenchymal stem cell therapy is unique because it uses the patient's own stem cells to potentially slow the progression of multiple system atrophy by providing neuroprotection and reducing inflammation, unlike traditional treatments that often have limited long-term benefits. ^{1 2 4 5 9}

What is the purpose of this trial?

The purpose of this study is to determine whether mesenchymal stem cells (MSCs) can be safely delivered to the cerebrospinal fluid (CSF) of patients with multiple system atrophy (MSA). Funding Source - FDA OOPD.

Research Team

Wolfgang Singer, MD

Principal Investigator

Mayo Clinic

Phillip A. Low, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for people aged 30-80 with multiple system atrophy (MSA), who meet specific clinical criteria and have a certain level of autonomic dysfunction. They should expect to live at least 3 more years, be able to consent, have normal cognition, and be within 4 years of MSA diagnosis. It excludes pregnant women not using birth control, those with unstable conditions or cancer, recent investigational drug use, medications affecting autonomic function, Parkinson-like diseases, dementia, brain surgery history for Parkinson's disease or contraindications for MRI.

Inclusion Criteria

I am between 30 and 80 years old and have been diagnosed with MSA.

Participants with an anticipated survival of at least 3 years in the opinion of the investigator

Participants who are willing and able to give informed consent

Exclusion Criteria

I am not on medications that affect my nervous system's automatic functions.

I have been diagnosed with cancer.

Women of childbearing potential who do not practice an acceptable method of birth control

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intrathecal doses of mesenchymal stem cells (MSCs) with varying dosages and schedules depending on the group assignment

6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in peripheral blood, CSF components, and nervous system structures using MRI

6 months

Treatment Details

Interventions

• Autologous Mesenchymal Stem Cells

Trial Overview The study tests if mesenchymal stem cells can be safely given into the cerebrospinal fluid of patients with multiple system atrophy. The goal is to see if this treatment is safe and how it affects the disease.

Participant Groups

Group I: 2 doses of 5 × 10(7) MSCs Experimental Treatment 1 Intervention

Group 2: Participants will receive one intrathecal dose of 5 × 10(7) mesenchymal stem cells (MSCs), followed by a second intrathecal dose of 5 × 10(7) MSCs approximately one month later

Group II: 2 doses of 1 × 10(8) MSCs Experimental Treatment 1 Intervention

Group 3: Participants will receive one intrathecal dose of 1 × 10(8) mesenchymal stem cells (MSCs), followed by a second intrathecal dose of 1 × 10(8) MSCs approximately one month later

Group III: 10 doses of 5 x 10(7) (±20%) MSCs Experimental Treatment 1 Intervention

Group 4: Participants will receive up to 10 doses of 5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.

Group IV: 10 doses of 2.5 x 10(7) (±20%) MSCs Experimental Treatment 1 Intervention

Group 5: Participants will receive up to 10 doses of 2.5 x 10(7) (±20%) mesenchymal stem cells (MSCs) approximately 6 months apart.

Group V: 1 dose of 1 × 10(7) MSCs Experimental Treatment 1 Intervention

Group 1: Participants will receive a single intrathecal dose of 1 × 10(7) mesenchymal stem cells (MSCs)

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Findings from Research

In a study involving 33 patients with MSA-C, those treated with autologous mesenchymal stem cells (MSC) showed a smaller increase in neurological deficits over 360 days compared to the placebo group, indicating potential efficacy in slowing disease progression.

MSC treatment was generally safe, with no serious adverse effects directly linked to the therapy, although some patients experienced small ischemic lesions from the intra-arterial infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of mesenchymal stem cells in multiple system atrophy. Lee, PH., Lee, JE., Kim, HS., et al.[2022]

In a study using a transgenic mouse model of multiple system atrophy (MSA), transplantation of human adipose-derived stem cells (ADSCs) significantly improved motor performance, indicating potential therapeutic benefits for MSA.

The mechanism of action for ADSC therapy appears to involve enhancing dopamine pathways, promoting autophagy to clear harmful proteins, reducing inflammation, and improving cell survival and myelination in the affected brain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of Adipose-Derived Stem Cells Alleviates Striatal Degeneration in a Transgenic Mouse Model for Multiple System Atrophy. Chang, C., Liu, JW., Chen, BC., et al.[2021]

Mesenchymal stem cells (MSCs) showed a significant protective effect against dopaminergic neurodegeneration in a model of multiple system atrophy (MSA), improving behavioral disorders and preventing neurodegeneration after transplantation.

The mechanism of MSCs involves modulating the expression of specific proteins, such as reducing polyamine modulating factor-binding protein 1 (PMFBP1) and altering 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL) levels, which are linked to neuronal protection against damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of multiple system atrophy using human bone marrow-derived mesenchymal stem cells by reducing polyamine and cholesterol-induced neural damages. Park, KR., Hwang, CJ., Yun, HM., et al.[2021]

In a 12-month study involving 11 patients treated with mesenchymal stem cells (MSCs) and 18 control patients with multiple system atrophy (MSA), MSC therapy led to significant improvements in neurological function as measured by the unified MSA rating scale (UMSARS).

The MSC-treated patients showed enhanced brain activity in areas related to motor function, with no serious adverse effects reported, indicating that MSC therapy is both safe and potentially effective in slowing MSA progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Lee, PH., Kim, JW., Bang, OY., et al.[2016]

The study evaluated the safety and efficacy of autologous adipose-derived stem cell (ASC) therapies in 17 patients with severe conditions, finding no serious adverse events over a follow-up period of up to 54 months.

Both ASC-derived products—a scaffold-free osteogenic graft for bone non-union and a biological dressing for chronic wounds—were successfully manufactured and implanted without contamination or genomic issues, demonstrating their feasibility for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications. Vériter, S., André, W., Aouassar, N., et al.[2022]

A review of 2,011 injections of autologous mesenchymal stem cells (AMSCs) for treating arthritis found no specific adverse events, indicating that these injections are completely safe.

The study concluded that AMSCs do not pose an increased risk of complications such as infections or tumor formation compared to traditional arthritis treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of Autologous Mesenchymal Cells for the Treatment of Arthritis. Prodromos, C., Rumschlag, T.[2021]

Intravenously applied mesenchymal stem cells (MSCs) in a mouse model of multiple system atrophy (MSA) showed significant neuroprotection in the substantia nigra and reduced neuroinflammation by downregulating various cytokines, indicating their potential as a therapeutic strategy.

Despite the neuroprotective effects observed, there were no improvements in behavioral outcomes, suggesting that while MSCs may help protect neurons, further research is needed to understand their overall efficacy in improving symptoms of MSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells in a transgenic mouse model of multiple system atrophy: immunomodulation and neuroprotection. Stemberger, S., Jamnig, A., Stefanova, N., et al.[2021]

References

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

A randomized trial of mesenchymal stem cells in multiple system atrophy. [2022]

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

Transplantation of Adipose-Derived Stem Cells Alleviates Striatal Degeneration in a Transgenic Mouse Model for Multiple System Atrophy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Bone-marrow-derived mesenchymal stem cell therapy for neurodegenerative diseases. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Prevention of multiple system atrophy using human bone marrow-derived mesenchymal stem cells by reducing polyamine and cholesterol-induced neural damages. [2021]

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

Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. [2016]

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

Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications. [2022]

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

Adipose-Derived Cells (Stromal Vascular Fraction) Transplanted for Orthopedical or Neurological Purposes: Are They Safe Enough? [2022]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Administration of Autologous Mesenchymal Cells for the Treatment of Arthritis. [2021]

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

Mesenchymal stem cells in a transgenic mouse model of multiple system atrophy: immunomodulation and neuroprotection. [2021]