Gene Therapy for Huntington Disease

Abstract

Englisch: Being one of the most common genetic neurodegenerative disease, Huntington's disease has been a model disease - also for gene therapy. Among the various options, the development of antisense oligonucleotides is the most advanced. Further options at the RNA level include micro-RNAs and modulators of RNA processing (splicing), at the DNA level zinc finger proteins. Several products are in clinical trials. These differ in their mode of application and in the extent of systemic availability. Another important difference between therapeutic strategies could be whether all forms of the huntingtin protein are targeted in the same extent, or whether a therapy preferentially targets particular toxic forms such as the exon1 protein. The results of the recently terminated GENERATION HD1 trial were somewhat sobering, most likely due to the side effect-related hydrocephalus. Therefore they represent just one step towards the development of an effective gene therapy against Huntington's disease.