Invention:
This invention comprises a series of novel small molecule compounds developed at the University of Arizona and their method of use for the treatment of locomotor dysfunction associated with Amyotrophic Lateral Sclerosis (ALS) and other diseases associated with proteinopathy of a transactive response (TAR) DNA binding protein, TDP-43. Testing in a previously developed Drosophila (fruit fly) model for ALS, these compounds rescued locomotor function. This invention has been shown to be effective in a fly model for rescuing locomotor dysfunction associated with TDP-43.
Background:
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder with currently no curative treatment that causes muscle weakness, disability, and eventually death, with a median survival rate of three to five years. TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, is the major disease protein in ALS. TDP-43 aggregation is linked with frontotemporal lobar degeneration and ALS; some neuroprotective drugs focus on the TDP-43 aggregation pathway as a means of treating ALS. The inventors previously developed a drosophila (fruit fly) model of ALS by over-expressing human TDP-43.
Applications:
- ALS therapeutics; reduction of locomotor dysfunction associated with ALS
- Treatment of other neurological disorders associated with TDP-43 and TARDBP dysfunction
Advantages:
- Demonstrated effectiveness in animal model
