Recent Advances in the Treatment of Huntington's Disease: Targeting DNA and RNA

CNS Drugs. 2020 Mar;34(3):219-228. doi: 10.1007/s40263-019-00695-3.

Abstract

Huntington's disease is a dominantly inherited neurodegenerative disease caused by an unstable expanded trinucleotide repeat at the short end of the fourth chromosome. Central nervous system pathology begins in the striatum, eventually affecting the entire brain and occurs consequent to multiple intracellular derangements. The proximate cause is a mutant protein with an elongated polyglutamine tract. Pharmacological approaches targeting multiple domains of intracellular functions have universally been disappointing. However, recent developments in gene therapy, including antisense oligonucleotides, small interfering RNAs, and gene editing are bringing new hope to the Huntington's community. This review discusses the promises and challenges of these new potential treatments.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA / genetics*
  • Gene Editing / methods
  • Genetic Therapy / methods
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics*
  • Oligonucleotides, Antisense / genetics
  • RNA / genetics*
  • RNA, Small Interfering / genetics

Substances

  • Oligonucleotides, Antisense
  • RNA, Small Interfering
  • RNA
  • DNA