Is mitochondrial oxidative metabolism the right therapy target in early Huntington disease?

Huntington disease (HD) is a progressive and fatal autosomal dominant neurodegenerative disorder characterized by extrapyramidal motor signs often preceded by cognitive and behavioral disturbances, with a prevalence of 5-10 cases per 100,000 people worldwide 1; expanded CAG repeats within the coding sequence of the HTT gene on chromosome 4p 2 are the cause. The gene encodes huntingtin (HTT), a ubiquitously expressed protein associated with most intracellular organelles. CAG repeats of 40 or more are associated with nearly full penetrance by age 65 years with a mean age at onset of 40 years and death 15-20 years later. 3 Although the function of HTT remains incompletely understood, HD likely arises from gain of function caused by the abnormal conformation of the mutant protein. 3