N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1900907 (2019)

A phase 1/2 trial of an antisense oligonucleotide that targets the messenger RNA of the gene causing Huntington’s disease shows that it is safe and has therapeutic potential.

Huntington’s disease onset occurs in mid to late life and is characterized by disordered movement, cognitive decline and other symptomatic behaviors. It is caused by a triplet repeat expansion in the Huntingtin gene, and it is thought that strategies to target and degrade this expansion could have therapeutic benefit.

In a randomized control trial of 46 individuals with Huntington’s disease, an antisense oligonucleotide targeting the triplet repeat expansion was injected into their spines. The trial showed that this approach is safe and that it resulted in reductions in the concentrations of the pathogenic protein.