While gene therapy is a burgeoning technique to treat a number of rare genetic conditions, there are still a few complexities associated with this treatment option. How safe and effective is it? What are the long-term implications of gene therapy? Will it confer sustained benefits? According to a press release from Sarepta Therapeutics (“Sarepta”), the company recently got to examine the longer-term benefits of its investigational gene therapy solution, SRP-9003, for patients with limb-girdle muscular dystrophy type 2E (LGMD2E). Data from their study suggests that SRP-9003 maintains responses even 2 years after treatment.

SRP-9003

To begin, what is SRP-9003? This gene therapy is currently in development. Altogether, it works by delivering a gene which codes for beta-sarcoglycan (beta-SG). Patients with LGMD2E lack beta-SG, causing progressive muscular degeneration. By providing patients with a functional gene via AAVrh74 vectors, SRP-9003 works to reverse this damage and promote strong muscular and skeletal health. SRP-9003 is administered intravenously.

In this study, researchers evaluated SRP-9003 in two cohorts dosed at either 1.85×10¹³ vg/kg or 7.41×10¹³ vg/kg respectively. 6 participants enrolled. The participants were aged 4-13. Data sourced from 12 and 24 months following treatment showed sustained beta-SG levels in both low and high dosage groups. Additionally, in the high dosage group, researchers also saw higher levels of delta-sarcoglycan (delta-SG) and gamma-sarcoglycan (gamma-SG). According to researchers, these suggest that SRP-9003 has an even more impactful reach.

Following 2 years of treatment, patients were able to improve on motor and muscle function. They were able to rise faster after sitting or laying down; climb stairs faster; and walk longer distances. Similar to prior research, SRP-9003 was found to be relatively safe and well-tolerated.

Limb-Girdle Muscular Dystrophy (LGMD)

Limb-Girdle muscular dystrophy (LGMD) falls into the larger umbrella of muscular dystrophy. In this particular form, the proximal muscles are affected. Proximal muscles are muscles closer to your body, such as those in your thighs, shoulders, pelvis, and upper arms. LGMD is characterized by progressive muscle weakness and degeneration. A variety of gene mutations cause LGMD and its various subtypes. For example, there is LGMD2A, LGMD2L, LGMD2C, and more.

In the specific form being treated by Sarepta, LGMD2E, SGCB gene mutations are usually the cause. LGMD2E is a severe form of LGMD inherited in an autosomal recessive pattern. Symptoms usually begin in childhood or early adolescence, with many culminating before a patient turns 10. Within as soon as 5 years or as late as 25 years, many patients require additional mobility assistance, such as wheelchairs. Symptoms vary. However, these may include:

• Progressive muscle weakness
• Abnormal or “waddling” gait
• Difficulty walking or running
• Increased calf muscle size
• Scoliosis (abnormal curvature of the spine)
• Cardiomyopathy (muscle weakness making it difficult to breathe)
• Intellectual or developmental delays