Centre for Medical Systems Biology director Gert-Jan van Ommen was granted €3 million of funding from the ZonMw Rare Disease programme to investigate new exon skipping applications for rare diseases. Exon skipping is a technique in which deleted or broken parts of the genome are skipped in order to influence the making of desired proteins, and prevent wrong proteins from being generated. This technique has been successfully ímplemented in treating Duchennes’ muscular dystrophy, and Van Ommen is now going to investigate its use for other diseases.
Duchenne muscular dystrophy (DMD) is a form of muscular dystrophy which results in muscle degeneration and eventual death. The disorder is caused by a mutation in the dystrophin gene which codes for the protein dystrophin, an important structural component within muscle tissue that provides structural stability to the dystroglycan complex (DGC) of the cell membrane. Mutations in these kind of genes which code for specific proteins underly many genetic and acquired diseases. In a recent paper in Cell, Van Ommen and his collegueas present an overview of recent strategies and successes in modulating splicing therapeutically in clinical and preclinical contexts. Effective approaches include restoring open reading frames, influencing alternative splicing, and inducing exon inclusion to generate beneficial proteins and remove deleterious ones.
At the moment this technique is applied as an experimental treatment for Duchenne’s muscular dystrophy in close collaboration with the biotechnology company Prosensa Therapeutics, but in the future it may be possible to initiate (pre)clinical programs for other diseases, like Huntington’s disease and CADASIL, a rare disease leading to stroke and dementia.