Targeting Expanded Repeats by Small Molecules in Repeat Expansion Disorders

Mov Disord. 2021 Feb;36(2):298-305. doi: 10.1002/mds.28397. Epub 2020 Dec 7.


Recent technological advancements in genetic analysis have allowed for the consecutive discovery and elucidation of repeat expansion disorders: diseases caused by the abnormal expansion of repeat sequences in the genome. Many of these repeat expansion disorders are neurodegenerative movement disorders. Radical cures for these disorders have yet to be established. Although conventional treatments for repeat expansion disorders have mainly targeted the abnormal mRNA and proteins encoded by the affected genes, therapeutic approaches targeting repeat DNA, the root cause of repeat disorders, is also being explored in current research. In particular, a small molecule has been found that binds to abnormally expanded CAG repeats, the cause of Huntington's disease, and shortens them. Such small molecules targeting nucleic acids are expected to be developed into groundbreaking therapeutic drugs capable of ameliorating the symptoms of repeat expansion disorders and preventing their onset. © 2020 International Parkinson and Movement Disorder Society.

Keywords: Huntington's disease; naphthyridine-azaquinolone; nucleic acid-targeting small molecule; repeat instability; triplet repeat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genome
  • Humans
  • Huntington Disease* / genetics
  • Repetitive Sequences, Nucleic Acid
  • Trinucleotide Repeat Expansion / genetics