Lewy Body Dementia Center Without Walls (CWOW) (U54 Clinical Trial Not Allowed) | RFA NS 18 024

Opportunity Information: Apply for RFA NS 18 024

The Lewy Body Dementia Center Without Walls (CWOW) (U54 Clinical Trial Not Allowed) grant opportunity (RFA-NS-18-024) is a National Institutes of Health (NIH) cooperative agreement designed to build a highly coordinated research center focused on the molecular forms of two key proteins implicated in Lewy Body Dementia (LBD): alpha-synuclein and amyloid-beta. The core purpose is to move beyond broad labels like "alpha-synuclein aggregates" or "amyloid plaques" and instead systematically define, in human LBD brain tissue, the specific subspecies (distinct biochemical or structural variants) of these proteins that exist in the disease. The expectation is that applicants will map out what forms are present, determine which forms are most toxic, explore how that toxicity happens, and clarify whether interactions between alpha-synuclein and amyloid-beta make disease worse or help explain why certain brain cell types or neural circuits are especially vulnerable.

A major emphasis of the FOA is the required use of human tissues, particularly post-mortem brain samples from people with LBD. Rather than relying primarily on animal models or simplified experimental systems, the initiative pushes teams to ground their work in human disease biology. The scientific goals are framed around three connected aims: first, comprehensive characterization of alpha-synuclein and amyloid-beta subspecies found in LBD brains; second, identification of the subspecies that are most toxic along with the cellular and molecular mechanisms driving that toxicity; and third, investigation of how alpha-synuclein and amyloid-beta may interact in ways that increase toxicity, accelerate pathology, or contribute to selective vulnerability across specific cells, brain regions, or circuits. The overall idea is that LBD pathology may not be driven by a single uniform "bad protein," but by a mixture of protein forms, some of which may be more damaging and may act synergistically when both protein systems are present.

Structurally, applications must be organized as a U54 Center-style program and are required to include at least three hypothesis-driven research projects. These projects should be distinct but integrated, collectively addressing the FOA's goals around protein subspecies characterization, toxicity, and protein-protein interactions. In addition to the research projects, applicants must include an Administrative Core to manage center operations, coordination, communication, and oversight. The FOA also allows (and in practice expects, when justified) additional cores as appropriate to support the scientific work, such as cores for tissue acquisition and processing, biochemistry and proteomics, structural biology, assay development, data management, or other shared resources needed to keep the center functioning as a unified "without walls" collaborative enterprise. The "Center Without Walls" concept signals that this is meant to be a networked, multi-team effort that may span multiple institutions, coordinated as a single center rather than as disconnected individual projects.

A standout deliverable required of all applications is a plan to develop a publicly available library of fully characterized alpha-synuclein and amyloid-beta subspecies found in LBD. This implies a community resource that goes beyond publishing results: it is intended to provide well-defined, accessible reference materials and/or datasets that other researchers can use to compare findings, validate assays, and accelerate biomarker and therapeutic discovery. In practical terms, this kind of library would likely include detailed characterization data (for example, biochemical properties, aggregation state, post-translational modifications, seeding activity, structural features, and associated toxicity readouts) and a clear framework for access and reuse by the wider research community. The FOA's insistence on public availability underscores NIH's broader goal of creating shared tools that make results reproducible and comparable across labs, which is especially important in fields where "aggregate" species can differ dramatically depending on preparation and measurement methods.

From an administrative standpoint, this opportunity is categorized as a discretionary funding program using a cooperative agreement mechanism, meaning NIH is expected to have substantial scientific or programmatic involvement during the award compared with a standard research project grant. The activity category is health, and the listing includes CFDA numbers 93.853 and 93.866. The funding opportunity was created on February 9, 2018, with an original closing date of April 30, 2018. The FOA title explicitly notes "Clinical Trial Not Allowed," which signals that the funded activities should not include clinical trials; the center's work is intended to be preclinical and mechanistic, anchored in human tissue-based molecular characterization and related experimental studies rather than interventional studies in living participants.

Eligibility is broad and includes many types of domestic U.S. organizations and some non-U.S. entities. Eligible applicants include state, county, and city 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; Native American tribal organizations other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those specific categories); for-profit organizations other than small businesses; and small businesses. The FOA also highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, 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 non-domestic (non-U.S.) entities (foreign organizations). This wide eligibility aligns with the "without walls" model, encouraging multidisciplinary, multi-institutional collaborations that can bring together neuropathology, protein chemistry, structural biology, systems neuroscience, and data/resource sharing under a single coordinated center.

Overall, this FOA is best understood as an NIH-driven push to standardize and deepen the field's understanding of the exact molecular species of alpha-synuclein and amyloid-beta that exist in human LBD and to connect those species to mechanisms of toxicity and vulnerability in the brain. By requiring multiple integrated projects, shared cores, and a public library of characterized protein subspecies, the program aims to create both new biological insight and durable community resources that can support downstream progress in diagnostics, biomarkers, and therapeutic strategy development for Lewy Body Dementia.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Lewy Body Dementia Center Without Walls (CWOW) (U54 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 2018-02-09.
• Applicants must submit their applications by 2018-04-30. (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 18 024

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