Mechanisms of Pathological Spread of Abnormal Proteins in LBD and FTD (R01 Clinical Trial Not Allowed) | RFA NS 21 006

Opportunity Information: Apply for RFA NS 21 006

The National Institutes of Health (NIH) funding opportunity titled "Mechanisms of Pathological Spread of Abnormal Proteins in LBD and FTD (R01 Clinical Trial Not Allowed)" (RFA-NS-21-006) supports research projects aimed at explaining how disease-associated, abnormal proteins propagate through the nervous system in Frontotemporal Dementia (FTD) and Lewy Body Dementia (LBD). The central scientific focus is on the biological mechanism or mechanisms that drive the movement and amplification of pathological proteins across brain regions, cell populations, and neural circuits, in ways that plausibly map onto how symptoms emerge and progress in patients. The announcement explicitly encourages applications that go beyond investigating a single, isolated mechanism and instead take a broader, more integrated view of how protein spread might occur when multiple proteinopathies, multiple cell or circuit types, and multiple biological pathways are involved.

In practical terms, this call is oriented around the idea that neurodegenerative dementias often show patterns that look like progressive dissemination rather than purely local injury, and the NIH is seeking mechanistic, hypothesis-driven studies that can clarify what enables that dissemination. Competitive projects would typically aim to identify the routes abnormal proteins take (for example, along defined neural connections, through extracellular spaces, via vesicle-mediated transport, or through cell-to-cell transfer), the cellular players that facilitate or resist propagation (such as specific neuronal subtypes, glial populations, or vulnerable circuits), and the molecular events that convert a local pathology into a spreading process. A major emphasis is placed on complexity and real-world disease context: proposals are especially welcome when they consider how spreading unfolds under conditions that resemble patient biology, including co-existing protein pathologies and heterogeneous cell environments, rather than assuming a single protein species moving through a uniform tissue landscape.

The mechanism uses the NIH R01 grant format, which is intended for substantial, multi-year research programs with well-developed aims, strong rationale, and rigorous methods. The "Clinical Trial Not Allowed" designation means the proposed work cannot include a clinical trial as defined by NIH policy, so applicants should plan for basic, translational, computational, or preclinical studies rather than interventional studies that prospectively assign human participants to an intervention to assess outcomes. Human-based research can still be relevant in many NIH programs, but under this specific notice the work needs to stay on the non-clinical-trial side of the line (for example, mechanistic analyses using existing human biospecimens or observational datasets may be possible depending on design, but not a prospective interventional trial).

Eligibility is broad and includes many kinds of U.S. and non-U.S. organizations. Eligible applicants span state, county, city, 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; other Native American tribal organizations; public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (excluding higher education institutions where applicable); for-profit organizations other than small businesses; and small businesses. The announcement also highlights additional eligible categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and foreign (non-U.S.) entities. This wide eligibility is meant to encourage participation from diverse institutions and research environments, including those serving underrepresented communities and those located outside the United States.

Administratively, this is a discretionary grant opportunity under the health funding activity category, with CFDA (now often referred to under Assistance Listings) numbers 93.853 and 93.866. The opportunity was created on August 6, 2020, and listed an original closing date of October 27, 2020. The listing does not specify an award ceiling or an expected number of awards in the provided source data, which generally means applicants would need to consult the full RFA and NIH institute guidance for budget expectations, project period norms, and review considerations.

Overall, the announcement is a targeted NIH R01 call aimed at deepening the field's mechanistic understanding of how abnormal proteins disseminate in LBD and FTD, with a clear preference for integrative proposals that treat propagation as a multi-factor process involving multiple proteins, multiple cell and circuit contexts, and multiple routes of spread. The ultimate value of this kind of work is that clarifying the rules and bottlenecks of pathological propagation can point to more precise therapeutic strategies, biomarkers, and staging frameworks, even when the immediate projects remain strictly non-clinical-trial research.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Mechanisms of Pathological Spread of Abnormal Proteins in LBD and FTD (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 2020-08-06.
• Applicants must submit their applications by 2020-10-27. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 21 006

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