Changing ATXN2 splicing reduced ALS-related TDP-43 damage in cells and mice
Original source
Splicing modulation of ATXN2 as a therapeutic strategy to regulate Ataxin-2 protein levels in ALS. (opens in a new tab)Compass summarised this from the study's abstract.
Study details
- Studied in
- Human, Mouse
Population inferred from the title and abstract by Compass.
Related topics
Researchers identified antisense oligonucleotides that alter ATXN2 RNA splicing and lower Ataxin-2 protein levels. In cell-based experiments, this reduced TDP-43 aggregation and stress-granule formation; in rNLS8 mice, lowering Ataxin-2 improved TDP-43 pathology. The findings support a proof-of-principle approach for ALS treatment.
Why this matters
ATXN2 is linked to ALS risk, and reducing its protein levels may lessen TDP-43-related damage in disease models. However, this work was conducted in cells and mice, so it does not yet show that the approach is safe or effective as a treatment for people with ALS.
Limitations and context
The evidence comes from human cell-based assays and an ALS mouse model, not from people with ALS. Further studies would need to establish whether the antisense oligonucleotides are safe, reach the relevant tissues, and improve outcomes in humans.