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

FAQs: NIH RFA-NS-19-027 (UG3/UH3) - Next-Generation Human 3D Cellular Models for ADRDs

What is the main goal of this NIH funding opportunity (RFA-NS-19-027)?

The opportunity supports the creation of next-generation, human, three-dimensional (3D) cellular model systems for Alzheimer's disease-related dementias (ADRDs). The intent is to fund teams that can build, rigorously characterize, and validate innovative human cell-based models that reproduce key disease features observed in people, rather than relying on simplified cell culture systems.

What kinds of projects is the FOA trying to encourage?

The FOA is designed to push the field toward model systems that better mirror real ADRD biology. Projects are expected to develop human 3D models that can be used to probe disease mechanisms more realistically and help identify credible therapeutic targets grounded in human-relevant biology.

Are clinical trials allowed under this announcement?

No. Clinical trials are not allowed under this FOA. The work is intended to stay in the preclinical/model-development space and not involve testing interventions in human participants.

What does "next-generation, human, three-dimensional cellular model systems" mean in this FOA?

Based on the description provided, it refers to human cell-based models built in 3D formats (tissue-like systems) that aim to reproduce ADRD-relevant features observed in people. The emphasis is on innovation, rigorous characterization, and validation, not simply constructing a 3D culture for its own sake.

Does the FOA require models to include more than one cell type?

Yes. A defining expectation is that the proposed models represent the complexity of ADRDs by incorporating multiple relevant human cell types within each model rather than focusing on a single cell population.

What ADRD features should the models aim to reproduce?

The FOA emphasizes reproducing phenotypic, mechanistic, and neuropathological hallmarks of ADRDs. It also specifically highlights the importance of capturing multi-faceted proteinopathies typical of ADRDs (including complex, interacting pathological protein processes) and/or vascular pathology, reflecting the view that dementia biology extends beyond neurons alone.

Does the FOA prioritize models that include vascular pathology?

The FOA explicitly emphasizes multi-faceted proteinopathies and/or vascular pathology. This signals strong interest in models that can reflect cerebrovascular components when relevant, alongside neurodegenerative processes.

Is it enough to build a 3D tissue-like construct to meet the FOA expectations?

No. Success is described as more than building a 3D construct. The model is expected to reliably display disease-relevant traits that can be measured, reproduced, and used experimentally, with rigorous characterization and validation.

What funding mechanism is used for this opportunity?

This FOA uses the UG3/UH3 cooperative agreement structure, which typically involves a phased approach with clear milestones and substantial NIH program involvement.

What does it mean that this is a cooperative agreement (UG3/UH3)?

It indicates a phased award structure and significant NIH involvement. Early activities focus on development and initial validation, while later activities expand to deeper characterization and experimental perturbation of the established model systems.

What are applicants expected to do in years 3 through 5?

Years 3 through 5 are highlighted as the period when projects are expected to conduct extensive characterization and perturbation of the established cellular systems. This includes defining what the model does well, documenting limitations, and demonstrating that the system can be manipulated in scientifically interpretable ways.

What kinds of "perturbation" does the FOA anticipate?

The FOA describes perturbations in a preclinical context, such as genetic, molecular, environmental, or pharmacologic perturbations, used to probe mechanisms and generate interpretable insights into disease biology.

What is the intended outcome of funding under this FOA?

The intended outcome is a set of robust, validated human 3D model platforms that the broader research community can use to interrogate molecular disease mechanisms and nominate potential therapeutic targets. The goal is durable tool development rather than a single experiment or dataset.

What is the award ceiling listed for this FOA?

The listed award ceiling is $750,000.

How many awards does NIH expect to make under this announcement?

The number of expected awards is not specified in the provided information.

When was the FOA created, and what was the original closing date?

The FOA was created on January 29, 2019, and the original closing date listed is March 14, 2019.

What are the CFDA numbers associated with this opportunity?

The CFDA numbers listed are 93.350, 93.853, and 93.866.

What types of organizations are eligible to apply?

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 nonprofit categories); for-profit organizations other than small businesses; and small businesses.

Does the FOA explicitly include certain institution types (for example, HSIs or HBCUs)?

Yes. It 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.

Are non-U.S. (foreign) institutions eligible to apply directly?

No. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply directly under this FOA.

Can a U.S. organization apply if it has non-domestic components?

Non-domestic components of U.S. organizations are not eligible. However, foreign components are allowed as defined by the NIH Grants Policy Statement, meaning a U.S.-based applicant may be able to include certain foreign activities or collaborations if they meet NIH policy requirements.

What is meant by allowing "foreign components" while foreign institutions cannot apply?

As described, the applicant organization must be U.S.-based, but the project may include limited foreign activities or collaborations when they qualify as "foreign components" under NIH policy. This preserves U.S.-based eligibility while allowing certain scientifically justified international elements.

Is this opportunity described as discretionary, and what category is it listed under?

Yes. It is described as a discretionary NIH opportunity in the health category and is funded as a cooperative agreement.

What is the research focus area in plain terms?

The focus is building and validating human 3D, multi-cell-type model systems that better represent ADRD disease biology, including complex protein-related pathologies and/or vascular contributions, and then rigorously testing and characterizing those models to make them useful tools for mechanistic discovery and target identification.