Sarepta Therapeutics has reported positive preliminary results from its Phase I/IIa clinical trial evaluating MYO-101 gene therapy for limb-girdle muscular dystrophy (LGMD) type 2E.

MYO-101 is designed to transduce skeletal and cardiac muscle with a gene coding for the full-length, native beta-SG protein. The absence of this protein is known to be responsible for LGMD2E.

The compound uses AAVrh74 vector that can be systemically delivered to skeletal, diaphragm and cardiac muscle.

LGMD2E is a muscular dystrophy that causes neuromuscular symptoms, such as difficulty in running, jumping and climbing stairs. Symptoms typically appear before the age of ten and the condition currently lacks a treatment or cure.

“Our gene therapy constructs have now produced high levels of expression of the missing protein of interest.”

Preliminary data from the first cohort of patients aged 4-13 years revealed robust transduced beta-SG expression when treated with a 5x13vg/kg infusion of MYO-101. The protein was observed to be properly localised to the muscle sarcolemma.

The results also demonstrated 47% mean fibre intensity, robust beta-SG quantification and a significant reduction in serum creatine kinase (CK) levels.

Sarepta Therapeutics president and CEO Doug Ingram said: “Our gene therapy constructs have now produced high levels of expression of the missing protein of interest, and strong results in related biomarkers, in Duchenne and LGMD2E, both cruel, fatal genetic diseases.

“And these results have potential read through to our other 4 LGMD programmes and further validate our gene therapy approach.”

Increased levels of liver enzymes were observed in two trial participants. One of the patients also experienced related transient rise in bilirubin and was designated as a serious adverse event (SAE).

Upon treatment with supplemental steroids, the elevated live enzymes returned to baseline.