Development and Validation of Human Cellular Models for Alzheimer's Disease-Related Dementias (ADRD) (R01 - Clinical Trial Not Allowed) | RFA NS 24 032

Opportunity Information: Apply for RFA NS 24 032

The NIH funding opportunity RFA-NS-24-032, titled "Development and Validation of Human Cellular Models for Alzheimer's Disease-Related Dementias (ADRD) (R01 - Clinical Trial Not Allowed)," supports research projects that build and rigorously validate new human cell-based model systems for ADRD. The central goal is to create models that are more clinically and/or pathophysiologically relevant than what is commonly available today, meaning they should better reflect what is actually happening in human disease rather than relying on simplified or incomplete experimental systems. While the mechanism is an R01 research grant, the notice makes clear that clinical trials are not allowed under this opportunity, keeping the focus on preclinical, laboratory-based model development and validation work.

A major emphasis of this program is complexity and relevance. NIH is looking for novel human cellular models that capture the multi-faceted biology of ADRD, including the involvement of multiple cell types and interacting disease processes. In practical terms, that points toward approaches such as multi-cellular co-cultures, engineered systems that include neuron-glia interactions (for example, neurons with astrocytes, microglia, oligodendrocytes, or vascular-related cell types), or more advanced platforms such as organoids, assembloids, or microphysiological "organ-on-chip" style systems when they genuinely improve biological fidelity. The models are expected to address important gaps in current ADRD modeling, so proposals need to clearly justify what existing models fail to capture and how the new system will overcome those limitations in a meaningful way.

Another key requirement is validation, and the NOFO signals that validation should be more than a basic demonstration that cells can be grown or that a marker can be measured. Applicants are expected to build a validation plan that includes internal validation (showing the model is stable, reproducible, and performs consistently within the lab), face validity (showing the model displays features resembling ADRD as observed in people), construct validity (showing that underlying mechanisms or causal pathways match known or strongly supported disease biology), and predictive validity to the extent feasible (showing that the model responds to perturbations in a way that aligns with human evidence, such as known pathway manipulations or reference compounds where appropriate). The intent is to move the field toward model systems that can be trusted for decision-making in mechanistic studies and, ideally, in therapeutic discovery and prioritization.

The opportunity allows models to be developed and validated for two broad types of impact. One path is to support therapy development, which could include building platforms suitable for testing interventions, identifying or confirming drug targets, or improving the translational value of preclinical findings. The other path is to deepen understanding of human disease mechanisms, including mechanisms that help explain why some people are predisposed to developing neurodegenerative dementias. That wording leaves room for models that incorporate genetic risk, cellular aging-related features, diverse donor backgrounds, or environmental and inflammatory stressors, as long as the model is still clearly human-cell-based, mechanistically motivated, and convincingly validated.

NIH also encourages multidisciplinary teams, reflecting how challenging these models can be to design and verify. Strong applications will often combine expertise across stem cell biology, neuroscience, glial biology, bioengineering, omics and computational analysis, neuropathology, and assay development, with a clear plan for integrating these capabilities into a single coherent model and validation workflow. The NOFO additionally encourages leveraging existing NIH cell repository resources and depositing newly generated cell lines into those repositories. This highlights an expectation of community benefit and broader usability, so teams that plan for standardization, documentation, quality control, and sharing of new cellular resources are aligned with the program's direction.

Eligibility is broad and includes many U.S.-based organization types: state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (outside of higher education); for-profit organizations other than small businesses; small businesses; and other eligible entities. The NOFO also explicitly calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, eligible federal agencies, faith-based or community-based organizations, regional organizations, and U.S. territories or possessions. At the same time, non-U.S. entities (foreign organizations) are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. However, "foreign components" as defined in the NIH Grants Policy Statement are allowed, meaning a U.S. applicant organization may include certain international collaborations or activities if they meet NIH's definition and are properly justified and structured within NIH policy.

From an administrative standpoint, this is a discretionary grant opportunity run by the National Institutes of Health, with CFDA numbers 93.853 and 93.866 listed for program classification. The original closing date provided is October 21, 2024. The award ceiling is listed as $500,000, which indicates an upper bound on the amount of funding per award under the terms described in the notice. Overall, the opportunity is aimed at accelerating better human-relevant ADRD cellular platforms that can serve as credible, validated tools for understanding disease biology and improving the translation of therapeutic ideas before they reach human testing.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Development and Validation of Human Cellular Models for Alzheimer's Disease-Related Dementias (ADRD) (R01 - 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 2024-02-16.
• Applicants must submit their applications by 2024-10-21. (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 $500,000.00 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 RFA NS 24 032

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