Improving motor function in children with muscular dystrophy Gene therapy phase 1/2 clinical results

Sarepta Therapeutics, which specializes in the development of rare disease therapies, announced that its research type 2E limb-belt muscular dystrophy (LGMD2E) gene therapy SRP-9003 has received positive results in a phase 1/2 clinical studyIn patients receiving low-dose gene therapy, the motor function of the patient continued to improve one year after one treatmentPatients who received high-dose gene therapy showed improved tissue marker indicators and good safetylimb-belt muscular dystrophy is a type of genetic disorder that can lead to progressive weakness and wasting, with symptoms that initially begin with the muscles around the hips and shoulders and then develop into the muscles of the arms and legsType 2E limb-belt muscular dystrophy (LGMD2E, also known as beta-myopolysaccharide, or LGMDR4) is caused by mutations in the gene encoding beta-myosacin (beta-sarcoglycan), resulting in beta-myosacinl deficiency of the autosomal recessive genetic ally of the LGMD subtypePatients begin to develop neuromuscular symptoms before the age of 10, such as running, jumping and climbing stairsProgress estruding in adolescence to incapacity to walk and often leads to early deathLGMD2E currently has no cure or cureSRP-9003 is a genetically modified gene therapy that uses AAVrh74 carrier delivery to encode full-length beta-myopolysaccharidesThe AAVrh74 vector is capable of delivering genetically modified skeletal muscles, shin muscles and heart muscles throughout the body, making it an ideal candidate for the treatment of peripheral neuromuscular diseasesAAVrh74 has lower immunogenicity than other human AAV vectorsThe treatment also selected MHCK7 as a promoter to express the geneticmodificationDesigned to induce the maintenance of stable expression of GM in the heart, this is critical for patients with type 2E limb-belt muscular dystrophy, as many people die from lung or heart complicationsthe six patients who took part in the study were between the ages of 4 and 13They were divided into two groups of 3 patients and received low-dose (5x1013 vg/kg) and high-dose (2x1014 vg/kg) gene therapytrial results showed that in three patients treated with high doses of SRP-9003, a biopsy of muscle tissue showedan increased dose-dependence on beta-myostose levels in the patient's muscles compared to patients treated with low dose SRP-9003 according to the measurement of immune tissue chemistry, the number of positive muscle fibers expressed beta-myopolysaccharides in the patient's muscles reached 72% of the total, beta-myosacin expression level was 73% of normal tissue, and they were expressed in the correct part of the muscle fibers The levels of creatine kinase (CK) in the serum of patients were reduced by 89% compared to the baseline CK levels are biomarkers associated with muscle attach patients treated with low-dose gene therapy showed continuous improvement in all functional indicators over the year following treatment The assessment of patients using the North Star LGMD (NSAD) assessment method improved by an average of nearly 6 points over the course of a year This is a far cry from the natural history of the disease, which usually drops in the number of untreated patients over the course of a year ", "LGMD2E is a devastating neuromuscular disease that can cause severe disability in children At present, patients lack treatment options in addition to rehabilitation treatment Lead researcher Dr Jerry Mendell, of The National Children's Hospital, said: "We are pleased that these data show high levels of protein expression in children with LGMD2E due to GENETIC modification This brings us one step closer to providing patients with a treatment that improves prognosis and quality of life "
Sarepta currently has five LGMD gene therapy projects under development for THE treatment of LGMD subtypes including LGMD2E, LGMD2D2D, LGMD2C, LGMD2B and LGMD2L