Recent therapeutic prospects for Machado-Joseph disease

Curr Opin Neurol. 2020 Aug;33(4):519-526. doi: 10.1097/WCO.0000000000000832.


Purpose of review: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is a fatal, dominantly inherited, neurodegenerative disease caused by expansion of a CAG repeat in the coding region of the ATXN3 gene. No disease-modifying treatment is yet available for MJD/SCA3. This review discusses recently developed therapeutic strategies that hold promise as future effective treatments for this incurable disease.

Recent findings: As a result of the exploration of multiple therapeutic approaches over the last decade, the MJD/SCA3 field is finally starting to see options for disease-modifying treatments for this disease come into view on the horizon. Recently developed strategies include DNA-targeted and RNA-targeted therapies, and approaches targeting protein quality control pathways and cellular homeostasis.

Summary: While still in preclinical testing stages, antisense oligonucleotides, short hairpin RNAs and citalopram all show promise to reaching testing in clinical trials for MJD/SCA3. Two pharmacological approaches in early stages of development, the slipped-CAG DNA binding compound naphthyridine-azaquinolone and autophagosome-tethering compounds, also show potential therapeutic capacity for MJD/SCA3. Overall, a handful of therapeutic options are currently showing potential as future successful treatments for fatal MJD/SCA3.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxin-3 / genetics*
  • Humans
  • Machado-Joseph Disease / drug therapy*
  • Machado-Joseph Disease / genetics
  • Naphthyridines / therapeutic use*
  • Quinolones / therapeutic use*


  • Naphthyridines
  • Quinolones
  • naphthyridine-azaquinolone
  • Ataxin-3