Recent therapeutic prospects for Machado–Joseph disease

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.

Source: Current Opinion in Neurology - July 30, 2020 Category: Neurology Tags: MOVEMENT DISORDERS: Edited by Nutan Sharma Source Type: research