Gene Therapy for Limb-Girdle Muscular Dystrophy

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sarepta Therapeutics, Inc.

Disqualifiers: Active viral infection, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but if you have a condition that requires ongoing treatment, it might be considered a risk for the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment SRP-9003 for Limb-Girdle Muscular Dystrophy?

Research on similar gene therapies for Limb-Girdle Muscular Dystrophy shows promising results, with improvements in muscle function and structure in animal models. These studies suggest that gene therapy can effectively restore muscle protein function and improve muscle health, which supports the potential effectiveness of SRP-9003. ^{1 2 3 4 5}

Is gene therapy for limb-girdle muscular dystrophy safe?

Gene therapy using adeno-associated virus (AAV) vectors has shown promise in early studies, with reports of effective gene delivery and no evident toxicity in muscle tissues. However, ongoing research emphasizes the need for careful management of potential side effects and immune responses to ensure safety. ^{1 2 3 6 7}

How is the treatment SRP-9003 unique for limb-girdle muscular dystrophy?

SRP-9003 is a gene therapy that uses a virus to deliver a healthy version of the gene responsible for limb-girdle muscular dystrophy type 2C/R5, aiming to restore muscle function by correcting the underlying genetic defect, which is different from traditional treatments that do not address the genetic cause. ^{1 2 3 8 9}

What is the purpose of this trial?

This trial tests SRP-9003, a gene therapy, in patients with LGMD2E, a type of muscular dystrophy. The therapy uses a harmless virus to deliver a healthy gene into muscle cells to fix the genetic issue. SRP-9003 is a gene therapy that uses a harmless virus to deliver a healthy gene into muscle cells, a method previously demonstrated to be effective in treating muscular dystrophies.

Research Team

Medical Director

Principal Investigator

Sarepta Therapeutics, Inc.

Eligibility Criteria

This trial is for males and females with Limb-Girdle Muscular Dystrophy, Type 2E (LGMD2E), who have specific gene mutations and experience difficulty in physical activities like running or climbing stairs. Participants must be able to complete a 100 meter walk/run test at a minimum of 40% efficiency compared to healthy individuals.

Inclusion Criteria

I can walk or run 100 meters at least 40% as well as others my age and size.

I am of any gender and ethnicity.

I have trouble running, jumping, or climbing stairs.

Exclusion Criteria

I don't have any illnesses or need for ongoing medication that would make gene therapy risky.

My heart's pumping ability is below 40%.

I have been diagnosed with or am being treated for an autoimmune disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of SRP-9003

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Multiple visits (in-person)

Treatment Details

Interventions

• SRP-9003

Trial Overview The study tests SRP-9003 (bidridistrogene xeboparvovec), which is a new gene therapy delivered once to patients with LGMD2E. It's an open-label trial, meaning both the researchers and participants know what treatment is being given.

Participant Groups

Group I: Cohort 2: SRP-9003 Experimental Treatment 1 Intervention

Participants will receive a single IV infusion of SRP-9003. Dose will be determined based on the findings from Cohort 1.

Group II: Cohort 1: SRP-9003 Experimental Treatment 1 Intervention

Participants will receive a single intravenous (IV) infusion of SRP-9003 at a prespecified dose.

Who Is Running the Clinical Trial?

Sarepta Therapeutics, Inc.

Lead Sponsor

Trials

54

Recruited

34,000+

Findings from Research

Gene therapy is showing promising progress in treating limb-girdle muscular dystrophies (LGMDs), particularly in conditions like calpainopathies, dysferlinopathies, and sarcoglycanopathies, with early clinical trials demonstrating safety and efficacy.

Emerging technologies such as CRISPR/Cas9 may further enhance the effectiveness of gene therapy for LGMDs, paving the way for more advanced treatment options in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unmet needs and evolving treatment for limb girdle muscular dystrophies. Pozsgai, E., Griffin, D., Potter, R., et al.[2022]

References

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

Unmet needs and evolving treatment for limb girdle muscular dystrophies. [2022]

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

Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A. [2012]

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

Systemic γ-sarcoglycan AAV gene transfer results in dose-dependent correction of muscle deficits in the LGMD 2C/R5 mouse model. [2023]

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

Gene Correction of LGMD2A Patient-Specific iPSCs for the Development of Targeted Autologous Cell Therapy. [2023]

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

Systemic delivery of AAVrh74.tMCK.hCAPN3 rescues the phenotype in a mouse model for LGMD2A/R1. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Gene therapy for primary myopathies: literature review and prospects. [2023]

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

Pharmacologic and genetic therapy for childhood muscular dystrophies. [2019]

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

Limb Girdle Muscular Dystrophies. [2020]

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

Restriction of calpain3 expression to the skeletal muscle prevents cardiac toxicity and corrects pathology in a murine model of limb-girdle muscular dystrophy. [2013]