Developing a genetic therapy for inherited diseases

About 6-8% of the population suffers from a rare disease, most of which are genetic and many of which have an unmet medical need. The genetic therapy for Duchenne muscular dystrophy, pioneered at the Leiden University Medical Center, might have therapeutic potential also for other genetic disorders.

In this project, three diseases were selected for which the therapeutic potential had been confirmed in early stage studies (cultured cells). The aim of the project was to optimize the technique for each disease and then assess whether the approach had a therapeutic effect in animal models, to allow a go/no go decision on whether to develop these approaches further towards clinical application, and if so to be able to select a lead compound. Furthermore, patent applications had to be maintained to allow potential future clinical developments.

We were able to optimize the compounds for all diseases except for CADASIL, where further optimization will be needed. For muscle diseases we had an unexpected finding: rather than the anticipated increase in muscle mass, a decrease was observed a decrease in muscle mass. While interesting scientifically, this had no therapeutic merit and the development of this compound has been stopped and the patents abandoned. For the other diseases results were more promising and follow up studies towards clinical trials have been initiated. This was a collaboration between the Leiden University Medical Center and Prosensa Therapeutics (now BioMarin).