Preclinical development of a small molecule inhibitor of tau self‐association for Alzheimer’s disease and related dementias

The approach for targeting toxic tau aggregates was to develop a small molecule inhibitor of tau self‐association that is agnostic to the types of aggregates formed. Pharmacodynamic studies of the lead compound in mouse models of tauopathy were performed. Therapeutic treatment of aged P301L tau JNPL3 mice showed reduced tau aggregation and improved motor behavior. Preventive treatment studies in young JNPL3 and htau mice with the lead also showed reduced tau aggregation. These results supported preclinical development of the lead to evaluate the potential of the compound for an Investigational New Drug Application (IND) submission to enable a first‐in‐human study.