Federal Grant Award Summary

Yale University received a $446,670 Project Grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), awarded May 6, 2026, with a completion date of June 30, 2028. The research project centers on the development and validation of bi-functional helical peptides designed to inhibit transactive response DNA binding protein 43 (TDP-43) aggregates, a key pathological feature in Alzheimer's disease and related dementias, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration.

The core deliverables include preclinical development activities examining target engagement, efficacy, and potential off-target effects of engineered helical peptide candidates both in vitro and in vivo. The research will test whether these peptides function as capping agents that inhibit TDP-43 fibril growth and facilitate clearance of peptide-bound aggregates through an integrated protein degradation motif. Research will be conducted at Yale University's Connecticut facilities and will advance understanding of TDP-43 mislocalization and aggregation mechanisms while generating preliminary data to support potential therapeutic development of peptide-based inhibitors for neurodegenerative diseases characterized by TDP-43 pathology.