Targeting The Root Cause of ALS, Pathogenic TDP-43
The formation of misfolded TAR DNA binding protein 43 (TDP-43) inside neurons is often associated with the development of amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia (FTLD), and limbic-predominant age-related TDP-43 encephalopathy (LATE).
TDP-43 is normally present in the nucleus of all cells and performs an essential role in neuronal cell survival. Therefore, the targeting of pathogenic TDP-43 requires strict selectivity for the misfolded form of the protein to potentially avoid safety concerns. Currently, we have several lead program candidates that have shown the desired selectivity for misfolded TDP-43 as well as an initial functional benefit in blocking prion-like propagation and/or clearing aggregated TDP-43 from cells.