Technologies

Invention

UA13-079 is a method for performing drug screens to test candidate compounds for their therapeutic effectiveness in treating locomotor and neurodegenerative defects in a drosophila model of the human disease Amyotrophic Lateral Sclerosis (ALS). The drug screen consists of testing the ability of candidate compounds to rescue deleterious phenotypic effects induced by mutations/functional alterations to TDP-43 in the drosophila model.

Background

Amyotrophic Lateral Sclerosis (ALS) is an adult onset, progressive neurological disorder characterized by selective degeneration and death of motor neurons in the motor cortex and the spinal cord. The ALS pathology includes ubiquitin positive cytoplasmic bodies, which have been shown to contain a 28 kDa fragment corresponding to the C-terminus domain of TDP-43 protein together with the full length TDP-43. Several missense mutations have been identified in TDP-43, the majority of which lie within the C-terminal region, indicating that this domain can be involved in the pathogenesis of ALS. Pathways and compounds with neuroprotective potential for TDP-43-associated phenotypes can be determined, which can impact a wide spectrum of ALS cases. Despite advances in understanding the physiology and pathophysiology of amyotrophic lateral sclerosis, there is still a scarcity of compounds that are potent, efficacious, and safe in the treatment or amelioration of amyotrophic lateral sclerosis.