Stem Cell Therapy for Multiple System Atrophy

Overseen By Tonette Gehrking

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Anticoagulants, Anti-Parkinsonian

Disqualifiers: Pregnancy, Cancer, Autoimmune, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 months

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for multiple system atrophy (MSA), a serious condition affecting movement and body functions. The study tests whether autologous mesenchymal stem cells can safely manage symptoms and slow disease progression. Participants will receive either the stem cell treatment or a placebo through spinal fluid injections. Suitable candidates have a clinical diagnosis of MSA and can walk at least 50 yards unassisted. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in MSA treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that could affect clinical evaluations, like levodopa and other anti-Parkinsonian drugs, at least four half-lives before study visits. The protocol does not specify about other medications, so it's best to discuss your specific situation with the study team.

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

Research has shown that using autologous mesenchymal stem cells, derived from one's own body, is generally safe for humans. In one study, researchers injected these stem cells into the spinal fluid of patients with multiple system atrophy (MSA), and the treatment was well-tolerated. Another study found that repeated use of these cells did not cause major side effects or harm. Most participants in these studies did not experience serious problems after treatment. While this is encouraging, each person's experience can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MSA?

Most treatments for Multiple System Atrophy, like medications that manage symptoms or physical therapies, aim to relieve symptoms without addressing the underlying disease. But this stem cell therapy uses autologous mesenchymal stem cells, which are derived from the patient's own body, offering a personalized approach. Researchers are excited because these stem cells have the potential to repair or replace damaged cells in the nervous system, potentially slowing or even reversing disease progression. Additionally, the intrathecal delivery method directly targets the central nervous system, which is where the damage occurs in this condition. This targeted approach could lead to more effective outcomes than the current standard treatments.

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

Research has shown that using a person's own stem cells might help treat multiple system atrophy (MSA). In this trial, one group of participants will receive autologous mesenchymal stem cells directly into their spinal fluid. In earlier studies, patients who received these stem cells showed improvements in movement-related symptoms. Another study found that repeated doses of these stem cells improved symptoms in patients with conditions similar to MSA. This treatment uses the patient's own stem cells, which might help slow the disease's progression. While more research is needed, these early results offer promise for people with MSA. ^{1 2 4 5 6}

Who Is on the Research Team?

Wolfgang Singer, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults aged 30-70 with Multiple System Atrophy (MSA) who can walk unaided and have a life expectancy of at least 3 years. They must have normal cognition, not be pregnant or breastfeeding, agree to birth control if applicable, and haven't taken investigational drugs recently. Excluded are those with MRI contraindications, unstable medical conditions, certain medication use, or severe heart, liver or kidney diseases.

Inclusion Criteria

I have been diagnosed with probable multiple system atrophy (MSA).

The doctor thinks you will live for at least 3 more years.

I can walk by myself for at least 50 yards and my UMSARS I score is between 5 and 17.

Exclusion Criteria

Pregnant or breastfeeding women, and women of childbearing potential who do not agree to practice an acceptable method of birth control. Acceptable methods of birth control in this study are: surgical sterilization, intrauterine devices, partner's vasectomy, a double-protection method (condom or diaphragm with spermicide), hormonal contraceptive drug (i.e., oral contraceptive, contraceptive patch, long-acting injectable contraceptive) with a required second mode of contraception

I do not have any major health issues that could interfere with the study.

Participants who have taken any investigational products within 90 days prior to baseline, or with expected effects lasting beyond 60 days prior to baseline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive intrathecal injections of 25 million mesenchymal stem cells or placebo at specified intervals

12 months

Injections at baseline, 3, 6, 9, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Clinical assessments at baseline, 3, 6, 9, and 12 months

Extension

Potential continuation of treatment based on interim analysis results

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Mesenchymal Stem Cells
• Placebo

Trial Overview This trial tests whether injecting patients' own mesenchymal stem cells into their spinal fluid is safe and effective for treating MSA. It's a randomized study where some get the real treatment while others get a placebo without knowing which one they received.

How Is the Trial Designed?

Group I: Arm 2 Active Control 2 Interventions

25 million mesenchymal stem cells administered intrathecally every 6 months for 2 injections (placebo injections at 3 month and 9 month timepoints)

Group II: Arm 1 Active Control 1 Intervention

25 million mesenchymal stem cells administered intrathecally every 3 months for 4 injections

Group III: Arm 3 Placebo Group 1 Intervention

Placebo (lactated Ringer's) administered intrathecally every 3 months for 4 injections

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

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]

Transplantation of human umbilical cord blood mononuclear cells (hUCB-MCs) via lateral atlanto-occipital space puncture (LASP) showed significant improvement in neurological function in seven patients with multiple system atrophy (MSA) over a follow-up period of 3 to 5 years, particularly noted at 3 to 6 months post-treatment.

The procedure was found to be safe, with no serious adverse events reported, indicating that hUCB-MC transplantation via LASP could be a viable long-term treatment option for MSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Efficacy of Human Umbilical Cord Blood Mononuclear Cell Transplantation by Lateral Atlanto-Occipital Space Puncture (Gong's Puncture) for the Treatment of Multiple System Atrophy. Gong, D., Wang, W., Yuan, X., 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]

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 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]

Autologous mesenchymal stem cell (aMSC) transplantation for multiple sclerosis (MS) patients is safe, with a transplant-related mortality rate of 0%, based on a meta-analysis of 9 studies involving 133 patients.

The treatment shows promising efficacy, with 72% of patients achieving no evidence of disease activity (NEDA) at 6 months and 62% at 1 year, particularly benefiting from intrathecal injections which were associated with lower rates of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Mesenchymal Stem Cell Transplantation in Multiple Sclerosis: A Meta-Analysis. Zhou, Y., Zhang, X., Xue, H., et al.[2020]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02315027

Mesenchymal Stem Cell Therapy in Multiple System Atrophy Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20523723

A Study to Evaluate Mesenchymal Stem Cells to Treat ... The purpose of this study is to assess optimal dosing frequency, effectiveness and safety of adipose-derived autologous mesenchymal stem cells delivered into ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6659003/

Intrathecal administration of autologous mesenchymal ... Methods. Utilizing a dose-escalation design, we delivered between 10 and 200 million adipose-derived autologous MSCs intrathecally to patients with early MSA.

4. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1257080/full

Long-term, repeated doses of intravenous autologous ... also demonstrated improvements in the clinical scores (UPDRS) using multiple infusions of adipose-derived MSCs in three PD patients (22).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05167721

Study Details | NCT05167721 | Randomized Double-Blind ... The purpose of this study is to assess optimal dosing frequency, effectiveness and safety of adipose-derived autologous mesenchymal stem cells delivered into ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10569690/

Long-term, repeated doses of intravenous autologous ... also demonstrated improvements in the clinical scores (UPDRS) using multiple infusions of adipose-derived MSCs in three PD patients (22).