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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safe delivery of mesenchymal stem cells (MSCs) to the cerebrospinal fluid to aid individuals with multiple system atrophy (MSA), a rare condition affecting movement and balance. The study involves different groups receiving various doses of MSCs to determine the most effective approach. It seeks participants diagnosed with MSA within the last four years whose daily lives are impacted by the condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using mesenchymal stem cells (MSCs) to treat multiple system atrophy (MSA) appears promising in terms of safety. In one study, injecting MSCs into the spinal fluid, using the patient's own cells, was well-tolerated by people with MSA, with no major safety issues, suggesting the treatment is generally safe. Another study that examined repeated doses of MSCs found improvements in related health conditions without significant side effects. These findings are encouraging and suggest that MSC therapy could be a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Multiple System Atrophy (MSA) focus on relieving symptoms rather than addressing the root cause. Researchers are excited about mesenchymal stem cell (MSC) therapy because it offers a new approach by potentially repairing and regenerating damaged tissues. Unlike traditional treatments, MSC therapy uses the body's own cells to promote healing, which may lead to improved function and slower disease progression. The therapy is delivered intrathecally, meaning directly into the spinal fluid, which allows for targeted action on the nervous system. This innovative method has the potential to transform how we manage MSA by offering more than just symptomatic relief.

What evidence suggests that this trial's treatments could be effective for multiple system atrophy?

Research suggests that mesenchymal stem cells (MSCs) might benefit people with multiple system atrophy (MSA). MSCs can repair and reduce damage in the body. Some early studies have shown that MSCs release substances that support nerve cells and reduce swelling, potentially slowing disease progression like MSA. This trial will administer different dosages of MSCs to participants to evaluate their effects. Patients in previous studies who received MSC treatment showed improvements in symptoms and overall abilities. However, more research is needed to confirm these promising results. ^{1 2 4 6 7}

Who Is on the Research Team?

Wolfgang Singer, MD

Principal Investigator

Mayo Clinic

Phillip A. Low, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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Mesenchymal Stem Cell Therapy in Multiple System Atrophy

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