Novel Small Molecules with Neuroprotective Potential in ALS and Related Neurodegenerative Diseases

This invention is a series of novel small molecule compounds developed at the University of Arizona that may be used in the treatment of Amyotrophic Lateral Sclerosis (ALS), particularly in treating the locomotor dysfunction associated with the disease. The compounds have a neuroprotective effect in that they prevent the aggregation of TDP-43, a neurotoxic protein associated with neurological disorders including ALS. This invention has been shown to be effective in a fly model for rescuing locomotor dysfunction associated with ALS.

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

Status: issued U.S. patent #11,147,795