In a recent press release, biotechnology company Sarepta Therapeutics announced positive findings from their clinical trial studying SRP-9003 as a treatment for limb-girdle muscular dystrophy (LGMD) type 2E. This investigational gene therapy showed significant improvement in patient outcomes.

SRP-9003: Clinical Trials

Gene Therapy

SRP-9003 is a gene therapy designed to improve muscle function in patients with LGMD type 2e. This form of muscular dystrophy is caused by a mutated SGCB gene, which prevents the production of a protein called beta-sarcoglycan. This protein plays a role in muscle health by stabilizing dystrophin, a protein that strengthens muscles. Without enough beta-sarcoglycan, dystrophin doesn’t function properly, leading to muscle weakness.

The therapy uses a modified (and harmless!) virus called AAVrh74 to deliver a functional copy of SGCB to skeletal, cardiac, and diaphragm muscles. Additionally, the gene therapy uses a MHCK7 promoter which helps control gene activity, increasing SGCB activity. Sarepta holds exclusive rights to this gene therapy program.

The Study

In this study, SRP-9003 was given intravenously to pediatric patients with LGMD type 2E. Overall, participant ages ranged from 4 to 13. The study is split into two cohorts: low-dose and high-dose, both of which included 3 participants.

Cohort 1, whose data was initially shared in 2019, received 1 infusion at 5×10¹³ vg/kg. Their data showed lowered levels of creatine kinase, an enzyme in the blood which suggests muscle damage. After 9 months, these 3 patients experienced better movement and function, including improvements in climbing and walking.

Cohort 2 received 1 infusion at a higher dose of 2×10¹⁴ vg/kg. In this group, patients saw an 89% reduction of creatine kinase. Additionally, muscle fiber strength and beta-sarcoglycan increased. One patient did experience a severe adverse reaction; they vomited for 3 days following their infusion, leading to dehydration. After 2 days of treatment, their condition improved.

Ultimately, the data highlights this gene therapy as a potentially effective and safe option for improving muscle function and quality of life in patients with LGMD type 2E.

Sarepta Therapeutics

Sarepta Therapeutics is a global biotech company whose focus is to develop genetic medicines and gene therapies for patients with rare diseases. Currently, Sarepta has 2 FDA-approved therapies for Duchenne muscular dystrophy (DMD). Additionally, they have 43 projects in their pipeline, including 5 gene therapy programs to address subsets of LGMD:

• LGMD 2E
• LGMD 2D
• LGMD 2C
• LGMD 2B
• LGMD 2L

Limb-Girdle Muscular Dystrophy (LGMD)

In this form of muscular dystrophy, characterized by progressive muscle loss and weakness, muscles in the shoulders and upper arms, pelvic area, and thighs are most affected. Currently, there is no cure for LGMD.

Symptoms may vary based on subset. In this case, symptoms for LGMD type 2E generally begin before the age of 10. Within years of diagnosis, many individuals require a wheelchair. They include:

• Difficulty running, walking, jumping, or climbing stairs
• Abnormal gait
• Delayed language development
• Intellectual and developmental delays
• Trouble standing after sitting
• Muscle weakness and eventual movement loss
• Scoliosis (as the condition progresses)
• Overly large calf muscles
• Weakening of the heart muscle (cardiomyopathy)
• Respiratory distress or failure
• Early mortality

Learn more about LGMD here.

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