1301-Clusterin Enhancers for Alzheimer’s Disease Therapy

This research presents the discovery of DDL-357, a novel small molecule designed to increase levels of secreted clusterin (sCLU) as a treatment for Alzheimer’s Disease. By utilizing high-throughput screening, the scientists identified BET inhibitors as potent enhancers of this neuroprotective protein, which helps clear toxic amyloid-β and tau aggregates. In animal studies, the lead candidate demonstrated excellent brain bioavailability and successfully improved memory and learning performance in mice. Further proteomic analysis revealed that the drug also supports mitochondrial function and synaptic plasticity, offering a multi-functional approach to halting neurodegeneration. These findings suggest that targeting sCLU enhancement provides a promising new therapeutic avenue that could complement existing Alzheimer’s treatments.

References:

• Cohn W, Campagna J, Wi D, et al. Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer’s disease mice[J]. npj Drug Discovery, 2025, 2(1): 7.