Treating the whole body in Huntington's disease

Lancet Neurol. 2015 Nov;14(11):1135-42. doi: 10.1016/S1474-4422(15)00177-5.

Abstract

Huntington'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. Links between peripheral biology and neurodegeneration have also been shown in other chronic neurodegenerative diseases, suggesting that modulation of these peripheral targets can offer new approaches to therapeutic development. Treatments targeted to tissues and organs outside the CNS might therefore substantially improve the quality of life of patients with Huntington's disease, even in the absence of disease-modifying effects.

Publication types

  • Review

MeSH terms

  • Blood
  • Central Nervous System / pathology*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / pathology*
  • Huntington Disease / therapy*
  • Liver / pathology
  • Muscles / pathology
  • Nerve Tissue Proteins / genetics
  • Peripheral Nerves / pathology

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins