Human Three-Dimensional Cell Model Systems for Alzheimers Disease-Related Dementias (ADRDs) (UG3/UH3 Clinical Trial Not Allowed) | RFA NS 19 027

Opportunity Information: Apply for RFA NS 19 027

This NIH funding opportunity (RFA-NS-19-027) supports the creation of next-generation, human, three-dimensional cellular model systems aimed at Alzheimers disease-related dementias (ADRDs). The central purpose is to fund teams that can build, rigorously characterize, and validate innovative human cell-based models that reproduce key disease features seen in people, not just in simplified cell cultures. The FOA is specifically trying to push the field toward models that better mirror real ADRD biology so researchers can probe disease mechanisms more realistically and identify credible therapeutic targets. Clinical trials are not allowed under this announcement, which signals that the work is intended to stay in the preclinical/model-development space rather than testing interventions in human participants.

A defining expectation is that the proposed models represent the complexity of ADRDs. That means incorporating multiple relevant human cell types within each model rather than focusing on a single cell population. The FOA emphasizes reproducing the multi-faceted proteinopathies typical of ADRDs (for example, complex interacting pathological protein processes) and/or vascular pathology, reflecting growing recognition that dementia biology involves more than neurons alone. In practice, this steers applicants toward systems that can capture interactions among cell types and pathological pathways that unfold together in human disease, including neurodegenerative and cerebrovascular components when relevant. The models are expected to recapitulate phenotypic, mechanistic, and neuropathological hallmarks of ADRDs, so success is not just building a 3D tissue-like construct, but showing it reliably displays disease-relevant traits that can be measured, reproduced, and used experimentally.

The award uses the UG3/UH3 cooperative agreement structure. This typically indicates a phased approach with clear milestones and substantial NIH program involvement. Early work is geared toward development and initial validation, while later work expands into deeper, more extensive characterization and experimental perturbation. In this FOA, years 3 through 5 are highlighted as the period when projects are expected to conduct extensive characterization and perturbation of the established cellular systems. In other words, investigators are expected not only to build the model, but to stress-test it scientifically: define what it does well, document its limitations, and demonstrate that it can be manipulated in ways that reveal interpretable disease mechanisms (for example, through genetic, molecular, environmental, or pharmacologic perturbations in a preclinical context). The end goal is a set of robust model platforms the broader research community can use as tools to interrogate molecular disease mechanisms and nominate potential therapeutic targets grounded in human-relevant biology.

Administratively, this is a discretionary NIH opportunity in the health category, funded as a cooperative agreement. The CFDA numbers listed are 93.350, 93.853, and 93.866. The FOA was created on January 29, 2019, with an original closing date of March 14, 2019, and it lists an award ceiling of $750,000. The number of expected awards is not specified in the provided source text.

Eligibility is broad and includes many types of domestic U.S. organizations and governmental entities. Eligible applicants include state, county, city or township, and 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; Native American tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (as long as they are not institutions of higher education in those categories); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, eligible federal agencies, Indian/Native American tribal governments other than federally recognized, and U.S. territories or possessions.

At the same time, the FOA draws clear boundaries around foreign involvement. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply directly, and non-domestic components of U.S. organizations are also not eligible. However, foreign components are allowed as defined by the NIH Grants Policy Statement, meaning a U.S.-based applicant can potentially include certain foreign activities or collaborations if they meet NIH rules for foreign components. This setup keeps the applicant organization U.S.-based while still allowing limited, policy-compliant international elements when scientifically justified.

Overall, the opportunity is designed to accelerate model innovation for ADRDs by funding multi-cell-type, human 3D systems that can capture complex disease biology, then subjecting those systems to rigorous characterization and experimental probing. The intended outcome is not a single experiment or dataset, but a set of validated, human-relevant model tools that can serve as a durable foundation for mechanistic discovery and therapeutic target identification across the dementia research community.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Human Three-Dimensional Cell Model Systems for Alzheimers Disease-Related Dementias (ADRDs) (UG3/UH3 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): 93.350, 93.853, 93.866.
• This funding opportunity was created on 2019-01-29.
• Applicants must submit their applications by 2019-03-14. (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 $750,000.00 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 19 027

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