Monday, June 05, 2023

Gene therapy for muscular dystrophy

Nature news reports on the upcoming FDA decision regarding the approval of the first gene therapy for muscular dystrophy.  A sample:

DMD seems like a straightforward target for gene therapy. The disease affects boys almost exclusively, because they have only one copy of the X chromosome, where the dystrophin gene is located; girls with a disease-causing variant have a backup copy. Replacing even some working protein in muscle cells should reverse the disease, or at least halt its progression.

But developing that replacement has proved difficult. Dystrophin is the longest gene in the human genome and is much too large to fit into the adeno-associated virus (AAV) vector commonly used to deliver gene therapies. Sarepta and several other companies have got around this by designing a gene that encodes just the most important parts of the protein (see 'Big genes in small packages'). The resulting ‘microdystrophin’ is only partly effective.