Mechanisms of Chimeric Cell Therapy in Duchenne Muscular Dystrophy

Abstract

Despite scientific efforts, there is no cure for Duchenne muscular dystrophy (DMD), a lethal, progressive, X-linked genetic disorder caused by mutations in the dystrophin gene. DMD leads to cardiac and skeletal muscle weakness, resulting in premature death due to cardio-pulmonary complications. We have developed Dystrophin Expressing Chimeric (DEC) cell therapy, DT-DEC01, by fusing human myoblasts from healthy donors and from DMD patients. Preclinical studies on human DEC cells showed increased dystrophin expression and improved cardiac, pulmonary, and skeletal muscle function after intraosseous administration. Our clinical study confirmed the safety and efficacy of DT-DEC01 therapy up to 24 months post-administration. In this study, we conducted in vitro assays to test the composition and potency of DT-DEC01, assessing chimerism level and the presence of dystrophin, desmin, and myosin heavy chain. Myoblast fusion resulted in the transfer of healthy donor mitochondria and the creation of chimeric mitochondria within DT-DEC01. The Pappenheim assay confirmed myotube formation in the final product. This study highlights the unique properties of DT-DEC01 therapy and their relevance to DMD treatment mechanisms.

Keywords

• Dystrophin Expressing Chimeric (DEC) cells
• mitochondrial transfer
• chimeric mitochondria
• DMD therapy
• DEC mechanisms
• Duchenne muscular dystrophy (DMD)