Investigators:
Jeremy Linsley, Operant BioPharma
MassAITC Cohort: Year 4 (AD/ADRD)
Extracellular amyloid plaques and intraneuronal neurofibrillary tangles are two histopathological hallmarks of Alzheimer’s disease (AD) that interact during disease progression. However, the precise nature of their interaction and how they collectively drive AD pathogenesis remain unclear. Developing compounds and identifying therapeutic targets to block Tau-ABeta interactions could form the basis for therapies that halt AD progression, complementing current ABeta-focused therapeutics that show limited efficacy in slowing disease.
Progress in understanding the multifaceted dynamics of Tau-ABeta interactions has been hindered by the complexity of their spatial and temporal relationships. Operant BioPharma has developed technologies to resolve dynamic phenotypic changes over neurodegeneration’s slow timeline, which are critical for identifying pathways governing Tau-ABeta interplay. Using proprietary AI, we identify small-molecule compounds that uncouple the pathological synergy between Tau and APP (the precursor to ABeta), thereby blocking disease progression in human neurons and slowing AD-related neurodegeneration.
Our strategy prioritizes drug repurposing: identifying compounds already proven safe in clinical trials for non-AD indications, which could be rapidly repositioned for AD and other tauopathies. Concurrently, we generate a phenotypic embedding of small-molecule effects to elucidate structure-activity relationships (SARs) between efficacy, cytotoxicity, and Tau-ABeta modulation, enabling data-driven optimization of AD therapeutics.