Simultaneous and Synergistic Multi-Target Validation for Alzheimers Disease-Related Dementias (R61/R33 Clinical Trial not allowed) | PAR 23 195

Opportunity Information: Apply for PAR 23 195

The NIH funding opportunity PAR-23-195, titled "Simultaneous and Synergistic Multi-Target Validation for Alzheimers Disease-Related Dementias (R61/R33 Clinical Trial not allowed)," is aimed at pushing Alzheimers disease and Alzheimers disease-related dementias (AD/ADRD) drug discovery beyond the traditional one-target-at-a-time model. The central idea is that AD/ADRD biology is complex and involves interacting pathways, cell types, neural circuits, organ-level systems, and overlapping pathologies. Because of that complexity, the FOA is designed to support projects that deliberately evaluate multi-target strategies, either by developing a single drug or biologic that hits multiple relevant targets, or by advancing a combination approach that uses more than one therapy together. The emphasis is on synergy: not just adding effects from multiple targets, but demonstrating that working on them together produces a stronger or more meaningful disease-modifying impact than tackling each target independently, similar to how combination or multi-mechanism treatments have been transformative in infectious disease and cancer.

This is a phased, milestone-driven R61/R33 mechanism. The R61 is the early, exploratory stage where applicants are expected to test clear hypotheses about beneficial interactions among known targets and to dig into the mechanisms behind those interactions. In practice, this phase is meant to reduce uncertainty around whether the proposed targets truly interact in a way that is therapeutically actionable, and to generate the evidence needed to justify a more intensive validation effort. The follow-on R33 phase supports rigorous validation of the multi-target concept, with the intent of producing a well-supported package of results that can serve as a launch point for translational development. The FOA frames success as putting teams in a strong position to pursue the next step in translation, specifically calling out the NIH IGNITE program and similar translational funding mechanisms as logical next destinations once a multi-target strategy is convincingly validated.

A key boundary condition is that clinical trials are not allowed under this announcement. That means the work should remain preclinical or otherwise non-clinical in a way that does not meet NIH definitions of a clinical trial. The scientific scope is broad in terms of what "targets" can mean, extending beyond single proteins to include pathways, cell states, circuit-level dysfunction, system-level processes, and distinct but co-occurring pathologies that shape AD/ADRD. The FOA is essentially inviting applicants to propose rational combinations or multi-functional interventions, then systematically prove that the interactions are real, beneficial, and mechanistically understandable enough to merit future therapeutic development.

From an administrative standpoint, this is a discretionary grant program administered by the National Institutes of Health, within the health funding activity category, and associated with CFDA numbers 93.853 and 93.866. The listed award ceiling is $499,000. The opportunity was created on 2023-06-20, with an original closing date of 2023-09-15. While the notice references expected awards, the provided source text does not specify a number.

Eligibility is intentionally broad and includes many types of U.S.-based organizations: state, county, and city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations other than federally recognized tribal governments; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education when specified); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, certain tribal governments other than federally recognized, regional organizations, eligible federal agencies, and U.S. territories or possessions.

Foreign eligibility is more restrictive. Non-domestic (non-U.S.) entities and non-domestic foreign institutions are not eligible to apply as the applicant organization. Non-domestic components of U.S. organizations are also not eligible to apply. However, foreign components, as defined in the NIH Grants Policy Statement, are allowed, which typically means the project can include certain international elements or collaborations if structured as a foreign component under NIH policy rather than as a foreign applicant institution.

Taken together, the FOA is best read as an NIH effort to create a stronger evidence base for multi-target disease modification in AD/ADRD by funding a structured progression from mechanistic interaction testing (R61) to thorough validation (R33). The intended endpoint is not a clinical trial, but a compelling, well-validated multi-target therapeutic rationale and supporting data set that can feed directly into later-stage translational programs and eventual therapeutic development.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Simultaneous and Synergistic Multi-Target Validation for Alzheimers Disease-Related Dementias (R61/R33 Clinical Trial not allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853, 93.866.
• This funding opportunity was created on 2023-06-20.
• Applicants must submit their applications by 2023-09-15. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $499,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 23 195

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