A gene therapy for Duchenne muscular dystrophy (DMD) has halted muscle decline in mice and shown potential for muscle repair. DMD is caused by mutations in the dystrophin gene, which encodes a protein crucial for muscle structure and function. Without dystrophin, muscle fibers progressively degenerate and weaken. Gene therapy aims to replace the faulty gene, but the full-length dystrophin gene is too large to be delivered into cells.
Professor Jeffery Chamberlain from the University of Washington School of Medicine, senior author of a study published in *Nature*, likened the approach to "ordering a king-sized bed that won't fit through your front door, so we broke it up into smaller pieces and it assembles all by itself." Researchers used adeno-associated virus (AAV) vectors to deliver parts of the dystrophin gene into muscle cells, where the fragments reassemble to produce a functional protein. The modified virus does not cause disease in the recipient.
DMD primarily affects males, as the dystrophin gene is on the X chromosome, with symptoms appearing around age three. The disease eventually impacts heart and lung muscles, and current treatments only slow its progression, with patients often living into their 20s or 30s.
Previous gene therapies for DMD, such as Elevidys and CIFFREO, have focused on delivering a shortened version of dystrophin but have not significantly improved motor function. The new therapy, however, successfully expresses large genes by splitting the dystrophin gene into transportable parts, which are then reconstituted into a functional protein.
Human trials for this novel therapy are expected to begin in two years. The study's authors hope this method may reverse muscle wasting and restore healthy muscle tissue in DMD patients. Meanwhile, other research teams are developing CRISPR-based genome editing techniques to restore dystrophin production in mice.
Sources - https://www.progress.org.uk/gene-therapy-stops-and-may-reverse-muscular-dystophy-in-mice/
https://www.nature.com/articles/s41586-024-07710-8
