Astellas Gene Therapies is developing AT702, AT751 and AT753 for the treatment of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy in children, affecting approximately 1 in 3,500 to 5,000 male births with more than 300,000 patients living with the disease worldwide1. DMD is caused by mutations in the dystrophin gene, which encodes the protein dystrophin, a structural protein involved in maintaining muscle cell integrity. Patients with DMD usually develop muscle weakness in the early years of life and become wheelchair-bound in their early teens. As the disease progresses, patients typically develop respiratory, orthopedic and cardiac difficulties. Cardiomyopathy and breathing complications usually begin by the age of 20, and few individuals with DMD live beyond their thirties. There is no cure for DMD and while the use of corticosteroid regimens has been shown to delay progression, there are no satisfactory symptomatic or disease-modifying treatments.

Our investigational exon skipping gene therapy approach to treat DMD uses an AAV vector, encoding modified U7 small nuclear RNAs (snRNA), to deliver an antisense sequence designed to induce cells to skip over faulty or misaligned sections of genetic code in the dystrophin gene, with the goal of restoring meaningful levels of a functional dystrophin protein. For the treatment of DMD, this approach has the potential to provide significant advantages over microdystrophin gene replacement strategies that produce a substantially truncated protein, which may limit the degree and durability of disease correction, as well as existing antisense oligonucleotide (ASO) therapies whose efficacy is limited by poor biodistribution to muscle tissue.

Initial preclinical studies, conducted at Nationwide Children’s Hospital with scAAV9.U7.ACCA targeting exon 2 duplication, demonstrated robust proof-of-concept results with dose-dependent increases in production of wild type and near-wild type length dystrophin protein and improvements in muscle function2. NCH, in collaboration with Audentes (now Astellas Gene Therapies), recently initiated a first-in-human clinical trial of this novel gene therapy approach for DMD patients with a duplication of exon 2 in the DMD gene3.

These preclinical and ongoing clinical studies support future AAV-U7snRNA based exon skipping therapies.

In parallel, Astellas Gene Therapies is developing AT702, an AAV-antisense gene therapy, designed to induce exon 2 skipping for the treatment of DMD patients with duplications in exon 2 and mutations in exons 1 – 5 of the dystrophin gene.

Astellas Gene Therapies is also conducting preclinical work to advance AT751 and AT753, additional investigational exon skipping gene therapies to treat DMD patients with genotypes amenable to exon 51 and exon 53 skipping. Both AT751 and AT753 utilize the same vector construct backbone as AT702, a platform approach, enabling a potentially accelerated path into clinical development. With these initial programs, we are is targeting more than 25 percent of patients with DMD. We plan to leverage our exon skipping gene therapy platform to develop further product candidates to address up to 80 percent of DMD patients over time.


  1. Mendell JR, Shilling C, Leslie ND, et al. Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol 2012;71:304-313.
  2. Simmons, 2014; Flanigan, 2014; Wein, 2015
  3. NCT04240314