Clinical development of novel therapies for Duchenne muscular dystrophy—Current and future

Abstract

Duchenne muscular dystrophy (DMD), the most common muscle degenerative disease, is an X‐linked genetic disorder caused by the loss or reduction of dystrophin protein, resulting in progressive muscle wasting, and involving skeletal, cardiac, and respiratory muscles. There is currently no cure for DMD, and an anti‐inflammatory steroid is the conventional treatment to delay disease progression. Recently, several therapeutic approaches have been developed to improve patient quality of life and even to treat the underlying cause of the disease. These approaches include exon‐skipping, stop‐codon read‐through, vector‐mediated gene therapy, and stem cell transplantation. Exon‐skipping is one of the most promising techniques, and four exon‐skipping drugs have received approval, including NS‐065/NCNP‐01 (viltolarsen) in Japan and the USA. The read‐through drug, Ataluren, has received approval in the EU. Vector‐mediated therapy and cell transplantation are also attractive approaches, and currently, clinical trials are ongoing for some drugs. Furthermore, several studies have developed innovative approaches for DMD treatment, such as multiple exon skipping, gene editing using the CRISPR/Cas9 system, and mesenchymal stromal cell (MSC)‐ or inducible pluripotent stem cell (iPSC)‐based cell transplantation. In this review, we summarize current therapeutic approaches for DMD treatment.