Gene Therapy for Limb-Girdle Muscular Dystrophy

Recruiting at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Sarepta Therapeutics, Inc.

Must not be taking: Corticosteroids

Disqualifiers: Cardiac, Pulmonary, Hepatic, Renal, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have a condition that requires chronic drug treatment, it might be considered a risk for the study, so 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 other types of Limb-Girdle Muscular Dystrophy shows promising results, such as improved muscle function and reduced muscle damage in animal models. These findings suggest that gene therapy, like SRP-9003, could potentially be effective for treating muscle disorders. ^{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, there is a need for careful management of potential side effects and immune responses to ensure safety in humans. ^{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 only manage symptoms. ^{1 2 3 8 9}

What is the purpose of this trial?

The primary purpose of this study is to evaluate the safety of SRP-9003 and to quantify expression of β-SG in the skeletal muscle of participants with limb-girdle muscular dystrophy, type 2E/R4 (LGMD2E/R4). The study will include both ambulatory (Cohort 1) and non-ambulatory (Cohort 2) participants.

Research Team

Medical Director

Principal Investigator

Sarepta Therapeutics, Inc.

Eligibility Criteria

This trial is for individuals aged 4-50 with Limb Girdle Muscular Dystrophy, type 2E/R4 who are either non-ambulatory (can't walk) or ambulatory (can walk). They must have specific genetic mutations and be able to undergo muscle testing. Those with significant other illnesses, exposure to gene therapy, or conditions affecting protocol compliance cannot participate.

Inclusion Criteria

I am between 4 and 50 years old and cannot walk.

I have specific genetic mutations in the β-sarcoglycan gene.

I can participate in muscle strength tests.

Exclusion Criteria

Presence of any other clinically significant illness or medical condition, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, neuromuscular (other than LGMD2E/R4), or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for gene transfer or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability

I haven't had gene therapy or experimental drugs within the trial's time limits.

I cannot take corticosteroids due to health reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single IV infusion of SRP-9003 on Day 1

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• SRP-9003

Trial Overview The study tests the safety and effectiveness of SRP-9003, a gene transfer treatment aimed at expressing β-SG in skeletal muscles of LGMD2E/R4 patients. It includes two groups: one that can walk (Cohort 1) and one that cannot (Cohort 2), assessing how well the treatment works in each.

Participant Groups

Group I: SRP-9003 Experimental Treatment 1 Intervention

Participants will receive single IV infusion of SRP-9003 on Day 1.

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

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

3. 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]

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

Efficacy and muscle safety assessment of fukutin-related protein gene therapy. [2023]

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

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

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

Limb Girdle Muscular Dystrophies. [2020]