Federal Grant Award Summary

The National Institute on Aging awarded a $162,000 Project Grant to The Washington University (Office of Sponsored Research Services) under the Aging Research program (CFDA 93.866) for the period March 1, 2026, through February 28, 2029. The award supports research to identify and characterize novel therapy targets in TDP-43 proteinopathies—a class of neurodegenerative diseases characterized by aberrant nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43). This pathological hallmark is observed across multiple age-related neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

The research deliverables focus on advancing understanding of TDP-43 dysfunction mechanisms and developing therapeutic interventions with broad applicability across TDP-43 proteinopathies. The project builds on recent findings identifying genetic variants in ATXN3 (ataxin-3) as a novel genetic risk factor for ALS and demonstrating that modulation of ATXN3 substantially impacts TDP-43 pathology in multiple cell types, including human induced pluripotent stem cell (iPSC)-derived neurons and patient brain tissue. The research will leverage cell-based models and patient tissues to identify and validate therapeutic targets that could potentially slow or reverse TDP-43 dysfunction, thereby addressing a significant unmet need in treating multiple neurodegenerative diseases affecting older adults.