Developing life-changing gene therapies
Duchenne muscular dystrophy (DMD) is a rare genetic disorder, caused by mutations in the gene responsible for making dystrophin, a protein involved in protecting muscle cell structure and function.
DMD primarily affects males with approximately 1 in 3,500 to 1 in 5,000 boys affected worldwide. The absence of functional dystrophin protein in individuals with DMD results in cell damage during muscle contraction, leading to cell death, fibrosis, and inflammation in muscle tissues. Initial symptoms of DMD include muscle weakness that are often noticeable at an early age with diagnosis typically occurring by 5 years of age. Over time, individuals with DMD experience progressive muscle weakness and eventually lose the ability to walk. Respiratory and heart muscles are also affected, leading to difficulty breathing and the need for ventilator assistance, along with the development of cardiomyopathy.
There is presently no cure for DMD. Currently approved treatments either do not address the underlying cause of the disorder or are helpful only to a subset of patients with specific genetic mutations.
Our investigational gene therapy, RGX-202, utilizes REGENXBIO’s propriety NAV AAV8 vector to deliver a gene to muscle cells that encodes for microdystrophin, a shortened and functional version of dystrophin protein. Microdystrophin is targeted as the functional protein since the gene that encodes for full-length dystrophin is too large to fit into the AAV vector. The novel RGX-202 microdystrophin transgene includes coding regions that are designed to retain essential functional elements of naturally occurring dystrophin, including a unique C-Terminal (CT) domain for potential improved function. A well-characterized muscle-specific promoter (Spc12-5) is employed to potentially allow expression of microdystrophin in skeletal and heart muscles. We believe that once the AAV8 vector delivers the microdystrophin transgene to muscle cells, they could produce the microdystrophin protein, protecting the cells from damage and, ultimately, preserving muscle function in boys with DMD.
RGX-202 is in the preclinical phase of development. We plan to submit an Investigational New Drug (IND) application in mid-2021 to enable initiation of a first-in-human clinical trial in DMD.