Federal Cooperative Agreement Summary

Weill Medical College of Cornell University received a $3.25 million Cooperative Agreement from the National Institute on Aging under the Aging Research program (CFDA 93.866) awarded April 1, 2026, with completion scheduled for March 31, 2028. The institution will conduct a Phase 1A clinical safety and dose-ranging trial of an adeno-associated virus (AAV) vector delivering a modified apolipoprotein E (APOE) gene therapy to the central nervous system of APOE4 homozygous patients with early-onset Alzheimer's disease. The primary deliverables include obtaining regulatory approvals from the Food and Drug Administration (FDA Investigational New Drug Application), Institutional Review Board, biosafety committees, and Data Safety Monitoring Board; manufacturing clinical-grade AAVRH.10HAPOE2CH vector; and administering the therapeutic agent via cerebrospinal fluid injection to evaluate tolerability and determine the highest safe dose in study participants.

This cooperative agreement advances translational research in neurodegenerative disease by moving a promising preclinical therapeutic candidate into human testing. The research builds on prior studies demonstrating that the novel E2CH variant of APOE—combining the protective APOE2 allele with a gain-of-function Christchurch mutation—was superior to unmodified APOE2 in reducing both amyloid and tau pathology in animal models of APOE4-associated Alzheimer's disease. The award aligns with the National Institute on Aging's mission to identify prevention and treatment strategies for Alzheimer's disease and related dementias through biomedical research.