Chemical Fix For Rare Muscular Dystrophy Flaw

A molecule that blocks kinase enzymes could inspire treatments for a rare form of muscular dystrophy, Japanese scientists report (Nature Commun., DOI: 10.1038/ncomms1306).

Patients with severe muscular dystrophy lack dystrophin, a structural protein in muscle tissue. Those with a mild form of the disease make a semifunctional version of dystrophin  because their cellular machinery skips over a defective portion of the dystrophin gene.

Several groups are trying to treat muscular dystrophy by inducing this process, called exon skipping. Masatoshi Hagiwara of Kyoto University, Masafumi Matsuo of Kobe University, and colleagues found a patient with a rare mutation who produced tiny amounts of partially functional dystrophin and showed that TG003, a compound they found in a screen, enhanced the levels of exon skipping and dystrophin production already occurring in cells from that patient. They suggest the molecule works by preventing phosphorylation of proteins that regulate gene splicing.

TG003 works for a rare mutation, so it's likely to help a smaller fraction of muscular dystrophy patients than might antisense oligonucleotide approaches, says Gert-Jan B. van Ommen of Leiden University Medical Center in the Netherlands, whose team developed an antisense treatment currently in clinical trials to treat muscular dystrophy. He thinks TG003 will be useful as a tool for learning about gene splicing.