New gene therapy trial for X-linked myotubular myopathy offers hope to children

Ann & Robert H. Lurie Children's Hospital of Chicago is one of the few centers participating in ASPIRO, an international Phase 1/2 clinical trial of a gene therapy product called AT132 for X-linked myotubular myopathy – a rare disease characterized by severe muscle weakness, breathing difficulty and early death. The study uses a respiratory virus called adeno-associated virus that is genetically modified to not cause illness but deliver a functional copy of the MTM1 gene, which encodes a protein involved in the function of muscle cells. This gene is defective in myotubular myopathy. By targeting the genetic cause of the disease and replacing the dysfunctional gene, researchers hope to help patients gain muscle function.

Multiple studies in animal models of myotubular myopathy have demonstrated that a single administration of AT132 improved muscle function and survival rates with no significant safety findings. In one study, these effects have lasted over four years.

"We are very excited about the potential of this therapy since we have no treatments available for children with myotubular myopathy, only supportive care," said Nancy Kuntz, MD, Principal Investigator (PI) at Lurie Children's, Medical Director of Mazza Foundation Neuromuscular Program and Professor of Pediatrics and Neurology at Northwestern University Feinberg School of Medicine. "In preclinical studies, the treated animals started walking, eating on their own, and showed overall muscle strength and function, which was a remarkable transformation."

The open-label, ascending dose clinical trial will evaluate the safety and preliminary efficacy of AT132 in approximately 12 patients who are younger than 5 years of age. The gene therapy product will be administered intravenously.

"This trial offers substantial hope to children and families affected by this devastating disease," said Vamshi Rao, MD, co-PI at Lurie Children's and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "We are thrilled to be able to offer this cutting-edge treatment to our patients at Lurie Children's."