Out of one mutation, many Huntington's disease effects

Abstract

In a thoughtful and wide-ranging Personal View, 1 Carroll JB Bates GP Steffan J Saft C Tabrizi SJ Treating the whole body in Huntington's disease. Lancet Neurol. 2015; 14: 1135-1142 Scopus (104) Google Scholar Jeffrey Carroll and colleagues discuss the growing literature on peripheral manifestations of Huntington's disease. As they point out, a substantial amount of evidence suggests extra-CNS abnormalities in Huntington's disease. In retrospect, these results are not surprising in view of the wide expression of mutant huntingtin in the brain and many other organs. 2 Strong TV Tagle DA Valdes JM et al. Widespread expression of the human and rat Huntington's disease gene in brain and non-neural tissues. Nat Genet. 1993; 5: 259-265 Crossref PubMed Scopus (324) Google Scholar Carroll and colleagues suggest plausibly that these abnormalities represent opportunities for useful clinical interventions. Modification of some peripheral manifestations, notably inflammatory responses, changes in kynurenine metabolism, or liver dysfunction, could modulate relevant CNS processes. They also suggest that targeting peripheral processes, even if such interventions have no CNS effects, might produce useful symptomatic benefits. Treating the whole body in Huntington's diseaseHuntington's disease is a genetic neurodegenerative disorder with symptoms that are linked to the progressive dysfunction and neuronal death in corticostriatal circuits. The causative gene (mutated HTT) is widely expressed outside the CNS and several peripheral signs of disease, including weight loss and increased proinflammatory signalling, are often seen; however, their importance in the pathophysiology of Huntington's disease is not clear. Studies in animals have shown that features of the disease involving the CNS, including synapse loss and behavioural alterations, are susceptible to modulation by treatments that target tissues and organs outside the CNS. Full-Text PDF