Nature Medicine: gene therapy for Duchenne muscular dystrophy

January 29, 2020. Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease in children. Researchers from the Technical University of Munich (TUM) and other institutions have developed a gene therapy that can provide permanent relief for patients with DMD.

The dystrophin protein is key to muscle tissue regeneration. People with Duchenne muscular dystrophy lack this essential protein due to gene mutations, so their muscle cells degenerate over time and are gradually replaced by connective tissue and adipose tissue. DMD mainly affects males because the key mutation site is located on the X chromosome.

Scientists at TUM have, for the first time, successfully repaired the mutated dystrophin gene in pigs by optimizing the Crispr-Cas9 gene editing technology. Professor Wolfgang Wurst, a geneticist at TUM and the Helmholtz Zentrum München, said: "These gene scissors are very effective and can correct the dystrophin gene." Compared with diseased animals that did not receive the treatment, the treated animals were less susceptible to cardiac arrhythmia and had an increased life expectancy.

Cardiologist Professor Christian Kupatt said: "Muscle and heart cells are long-lived cell structures. Throughout the entire life cycle from birth to death, half of all cardiomyocytes can still maintain function. As long as the cell is alive, its genome can be used for protein biosynthesis; once the cell is affected by treatment, it will remain in the corrected state. Therefore, if we change the genome of cardiomyocytes, a long-term effect will be achieved." Source: 生物谷. Information source: New gene correction therapy for Duchenne muscular dystrophy. Original source: A. Moretti, L. Fonteyne, F. Giesert, P. Hoppmann, A. B. Meier, T. Bozoglu, A. Baehr, C. M. Schneider, D. Sinnecker, K. Klett, T. Fröhlich, F. Abdel Rahman, T. Haufe, S. Sun, V. Jurisch, B. Kessler, R. Hinkel, R. Dirschinger, E. Martens, C. Jilek, A. Graf, S. Krebs, G. Santamaria, M. Kurome, V. Zakhartchenko, B. Campbell, K. Voelse, A. Wolf, T. Ziegler, S. Reichert, S. Lee, F. Flenkenthaler, T. Dorn, I. Jeremias, H. Blum, A. Dendorfer, A. Schnieke, S. Krause, M. C. Walter, N. Klymiuk, K. L. Laugwitz, E. Wolf, W. Wurst, C. Kupatt. Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy. Nature Medicine, 2020; DOI: 10.1038/s41591-019-0738-2