The National Institute on Aging (NIA) has announced the funding opportunity titled Translational Bioinformatics and Experimental Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease and Related Dementias (R01 Clinical Trial Not Allowed) under funding opportunity number PAR-25-374. This funding initiative seeks to support preclinical research that integrates computational and experimental methodologies to evaluate drugs or drug combinations predicted to be effective in treating or preventing Alzheimer’s Disease (AD) and AD-related dementias (ADRD). The focus is on drug repositioning and combination therapy development using mouse models or cell-based systems to establish robust preclinical proof-of-concept evidence.

The primary purpose of this funding opportunity is to facilitate research that identifies and rigorously tests existing FDA-approved drugs, investigational drugs, or compounds from failed Phase II/III clinical trials that may have therapeutic potential for AD/ADRD. Research may also include evaluating these drugs in combination with non-pharmacological interventions such as exercise, diet, cognitive training, or sleep management. The central objective is to prioritize the most promising candidates using systems biology and multi-omics approaches, and validate their efficacy, pharmacodynamics, and toxicity profiles in preclinical models. Academic and industry partnerships are encouraged, particularly when industry partners can contribute legacy trial data, biosamples, or failed compounds.

Eligible activities include preclinical studies to determine drug efficacy, toxicity, target engagement, and mechanism of action; testing candidate drug combinations for synergistic effects or adverse events; evaluating blood-brain barrier permeability; and developing quantitative models for assessing therapeutic synergy. Research teams are expected to include multidisciplinary expertise in fields such as network biology, pharmacology, animal or cell-based models of AD, biostatistics, and clinical research. Projects must include clear go/no-go decision points to facilitate unbiased evaluation of therapeutic potential.

Eligible applicants include public and private higher education institutions, nonprofits, small businesses, for-profit organizations, local and tribal governments, and foreign organizations. Applicants are required to adhere to open-science principles, sharing data, methods, tools, and research outputs via publicly accessible platforms like the AD Knowledge Portal and adhering to FAIR (Findable, Accessible, Interoperable, Reusable) data principles. Preclinical efficacy studies must align with ARRIVE guidelines and best practices for AD preclinical research.

The funding opportunity has a budget cap of $1 million in direct costs per year, with a project duration limit of five years. The NIA intends to commit $6 million in Fiscal Year 2026 to fund approximately 4–5 awards. Applications must include comprehensive Data Management and Sharing Plans, detailing the strategy for making research outputs accessible and reusable by the broader scientific community. Projects must also follow rigorous standards for experimental design, analysis, and reporting to ensure reproducibility and transparency.

Applications are due by 5:00 PM local time of the applicant organization, with submission dates scheduled across multiple cycles from June 9, 2025, through February 7, 2028. Applicants are encouraged to contact NIA program staff early in the preparation process to ensure alignment with the goals of the funding opportunity. For further details, prospective applicants should review the full Notice of Funding Opportunity.