Broad spectrum TDP oligomer inhibitor

This program aims to develop a therapeutic for halting disease progression in Amyotrophic Lateral Sclerosis (ALS), by designing small molecules that inhibit the misfolding of TAR DNA-binding protein (TDP) isoforms in ALS and thereby halt further growth and pathology of neurotoxic aggregates.

Compounds experimentally assayed to date from the TREVENTIS compound collection have been identified as having anti-TDP oligomer activity in both turbidity and cell-based models. Three chemotypes have been identified that show favorable activity profiles. Many compounds show a profile of binding to all three TDP isoforms, which holds promise as a broad-spectrum anti-misfolding agent for TDPopathies.

Beyond ALS, this program is also of relevance to frontotemporal dementia (FTD) mediated by TDP. In 2022, Treventis received a $2.97M grant from the U.S. Department of Defense to support Treventis’ development of drugs against FTD.