Cell-Based Therapy for Duchenne Muscular Dystrophy

Overseen By Peter Kang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: HLA antibodies, Investigational therapy, Allergy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

8 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but you must be off investigational therapies for more than 30 days before joining.

What data supports the effectiveness of the treatment MyoPAXon for Duchenne Muscular Dystrophy?

Research on a similar treatment, DT-DEC01, shows that it improved muscle function and strength in Duchenne Muscular Dystrophy patients, as well as heart and lung function, without causing serious side effects. This suggests that MyoPAXon, which may have similar properties, could also be effective in treating this condition. ^{1 2 3 4 5}

Is cell-based therapy for Duchenne Muscular Dystrophy safe for humans?

The cell-based therapy, known as Dystrophin Expressing Chimeric (DEC) cell therapy, has been tested in humans with Duchenne Muscular Dystrophy and showed no adverse events or serious adverse events up to 22 months after administration. This suggests that the therapy is generally safe for humans. ^{2 5 6 7 8}

How is the treatment MyoPAXon unique for Duchenne Muscular Dystrophy?

MyoPAXon is a cell-based therapy that aims to increase dystrophin expression in muscles, which is crucial for improving muscle function in Duchenne Muscular Dystrophy. Unlike traditional treatments that only manage symptoms, this therapy uses muscle-derived stem cells to potentially restore muscle function and structure by promoting the growth of healthy muscle tissue. ^{1 8 9 10 11}

What is the purpose of this trial?

This is a single-center, single-arm, interventional phase 1 trial to evaluate the safety and tolerability of local injection of induced pluripotent stem cell (iPSC)- derived CD54+ allogeneic muscle progenitor cells in individuals with Duchenne muscular dystrophy (DMD)

Eligibility Criteria

This trial is for adults over 18 with Duchenne muscular dystrophy, confirmed by gene mutations or muscle biopsy. Participants must be non-ambulatory but have intact EDB muscles and off other investigational therapies for over 30 days. They should commit to birth control methods if applicable and consent to a long-term follow-up of 15 years.

Inclusion Criteria

Off investigational therapies for more than 30 days

Voluntary written consent from the subject or parent(s)/guardian(s) and assent from participant prior to the performance of any research related activity.

I cannot walk by myself.

Exclusion Criteria

Active treatment with another investigational therapy

Known allergy to MyoPAXon components

My body has antibodies against specific antigens on MyoPAXon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants are started on tacrolimus 1 week prior to dosing

1 week

Treatment

MyoPAXon is delivered via open intramuscular injection into a single EDB muscle as a one-time dose

1 day

Post-Treatment

Participants stay on the maintenance dose of tacrolimus on a BID schedule

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• MyoPAXon

Trial Overview The trial tests the safety of injecting stem cell-derived muscle progenitor cells into patients with DMD. It's an early-stage study (phase 1) focusing on how well participants tolerate this new cell-based therapy called MyoPAXon, alongside Tacrolimus to prevent rejection.

Participant Groups

Group I: Arm D: MyoPAXon 200 x 10^6 Experimental Treatment 2 Interventions

MyoPAXon will be delivered via open intramuscular (IM) injection into a single EDB muscle for each participant as a one-time dose. The participants will be started on tacrolimus 1 week prior to dosing and stay on the maintenance dose on a BID schedule for 3 months after injection

Group II: Arm C: MyoPAXon 100 x 10^6 Experimental Treatment 2 Interventions

MyoPAXon will be delivered via open intramuscular (IM) injection into a single EDB muscle for each participant as a one-time dose. The participants will be started on tacrolimus 1 week prior to dosing and stay on the maintenance dose on a BID schedule for 3 months after injection

Group III: Arm B: MyoPAXon 50 x 10^6 Experimental Treatment 2 Interventions

MyoPAXon will be delivered via open intramuscular (IM) injection into a single EDB muscle for each participant as a one-time dose. The participants will be started on tacrolimus 1 week prior to dosing and stay on the maintenance dose on a BID schedule for 3 months after injection

Group IV: Arm A: MyoPAXon 25 x 10^6 Experimental Treatment 2 Interventions

MyoPAXon will be delivered via open intramuscular (IM) injection into a single EDB muscle for each participant as a one-time dose. The participants will be started on tacrolimus 1 week prior to dosing and stay on the maintenance dose on a BID schedule for 3 months after injection

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Parent Project Muscular Dystrophy

Collaborator

Trials

7

Recruited

11,000+

Duchenne UK

Collaborator

Trials

2

Recruited

40+

Findings from Research

Transplantation of dystrophin-expressing chimeric (DEC) cells derived from myoblasts significantly increased dystrophin expression in the skeletal, cardiac, and respiratory muscles of a mouse model for Duchenne muscular dystrophy (DMD), leading to improved muscle function and reduced pathology.

The study demonstrated that DEC transplantation not only preserved heart function and respiratory capacity but also improved muscle strength and reduced inflammation and fibrosis, suggesting a promising new therapeutic approach for enhancing the overall health of DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human dystrophin expressing chimeric (DEC) cell therapy ameliorates cardiac, respiratory, and skeletal muscle's function in Duchenne muscular dystrophy. Siemionow, M., Langa, P., Harasymczuk, M., et al.[2022]

The DT-DEC01 cell therapy demonstrated a strong safety profile with no adverse events reported up to 21 months after administration, indicating it is a safe treatment option for patients with Duchenne Muscular Dystrophy (DMD).

Functional improvements were observed in patients, including better performance in the 6-Minute Walk Test and other assessments, suggesting that DT-DEC01 may effectively enhance muscle function and overall health in DMD patients over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. Siemionow, M., Biegański, G., Niezgoda, A., et al.[2023]

The first-in-human study of DEC cell therapy for Duchenne Muscular Dystrophy (DMD) showed no adverse events in the first 3 patients over 14 months, indicating a strong safety profile for this novel treatment.

Patients receiving DEC therapy demonstrated significant improvements in muscle function and strength, as measured by various functional tests, suggesting that this therapy could effectively enhance quality of life for DMD patients without the need for immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up. Heydemann, A., Bieganski, G., Wachowiak, J., et al.[2023]

The novel DT-DEC01 therapy, which uses Dystrophin Expressing Chimeric (DEC) cells, was found to be safe in a small study of 3 boys aged 6-15 years, with no therapy-related adverse events reported up to 22 months after treatment.

Preliminary efficacy was observed through electromyography (EMG) assessments, showing increased motor unit potentials in treated muscles at 12 months, indicating potential benefits for muscle function in boys with Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic-Intraosseous Administration. Niezgoda, A., Biegański, G., Wachowiak, J., et al.[2023]

A new immunodeficient rat model of Duchenne muscular dystrophy (DMD) was developed, showing similar disease characteristics to human patients, which is crucial for studying potential treatments.

Successful engraftment of human myoblasts in this rat model indicates its potential for preclinical studies on cell transplantation therapies for DMD, paving the way for future research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new immunodeficient Duchenne muscular dystrophy rat model to evaluate engraftment after human cell transplantation. Sato, M., Goto, M., Yamanouchi, K., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Human dystrophin expressing chimeric (DEC) cell therapy ameliorates cardiac, respiratory, and skeletal muscle's function in Duchenne muscular dystrophy. [2022]

2. Pakistan pubmed.ncbi.nlm.nih.gov

Episomal reprogramming of Duchenne muscular dystrophy patients derived CD3+ T cells towards induced pluripotent stem cells. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Experimental study of treating Duchenne muscular dystrophy with myoblast transplantation]. [2012]

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

Aggregate mesenchymal stem cell delivery ameliorates the regenerative niche for muscle repair. [2019]

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

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. [2023]

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

Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic-Intraosseous Administration. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A new immunodeficient Duchenne muscular dystrophy rat model to evaluate engraftment after human cell transplantation. [2023]

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

Myostatin genetic inactivation inhibits myogenesis by muscle-derived stem cells in vitro but not when implanted in the mdx mouse muscle. [2021]

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

Hematopoietic cell transplantation provides an immune-tolerant platform for myoblast transplantation in dystrophic dogs. [2021]

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

Evaluation of hiPSC-Derived Muscle Progenitor Cell Transplantation in a Mouse Duchenne Muscular Dystrophy Model. [2022]