Investigating inhibition of TDP-43 propagation as a therapeutic strategy for ALS

Project Overview

It is not known why ALS is a rapidly progressing disease. The discovery that the accumulation of TAR DNA-binding protein 43 kDa (TDP-43) is a pathological hallmark of sporadic ALS and a subset of frontotemporal lobar degeneration (FTLD) provides clues. TDP-43 is prone to incorrect folding and it has been proposed that the protein may spread through the nervous system and contribute to ALS pathology. We will use animal and cell culture models to study the propagation of TDP-43 in neurons and find drugs that block this transmission. We hypothesize that small-molecule mediated inhibition of TDP-43 spreading will block motor neuron degen-eration and may be a therapeutic approach for ALS.

Partners and Donors

ALS Society of Canada