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 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.