Natural History and Biomarker Studies of Rare Neurodegenerative Diseases (U01) Clinical Trials Optional | RFA FD 23 028

Opportunity Information: Apply for RFA FD 23 028

The grant opportunity titled "Natural History and Biomarker Studies of Rare Neurodegenerative Diseases (U01) Clinical Trials Optional" (Funding Opportunity Number RFA-FD-23-028) is a discretionary funding program from the U.S. Department of Health and Human Services, Food and Drug Administration (FDA). It uses a cooperative agreement mechanism (U01), which typically means the FDA plans to have substantial involvement during the project rather than acting only as a passive funder. The program sits in the broader activity category of consumer protection, science and technology, and research and development, and it is associated with CFDA number 93.103. The opportunity was created on February 27, 2023, with an original application due date of May 4, 2023.

At its core, this FOA is designed to strengthen the evidence base for rare neurodegenerative diseases by funding well-constructed prospective natural history studies and/or biomarker studies. The emphasis on prospective work matters because it prioritizes forward-looking, systematically collected data rather than relying only on retrospective chart reviews or fragmented datasets. The target population includes both children and adults, reflecting the fact that rare neurodegenerative disorders can present across the lifespan and often require age-appropriate measures of disease onset, progression, and clinical impact.

The FDA is aiming to fund studies that directly address unmet needs and major knowledge gaps that slow down therapy development in rare neurodegeneration. In practical terms, natural history studies help clarify how a disease typically progresses over time, what clinical milestones occur and when, how variable the disease is across patients, and what outcomes are most meaningful and measurable. Biomarker studies focus on identifying and characterizing measurable indicators (for example, imaging measures, blood or CSF markers, digital measures, or other objective signals) that track disease presence, severity, progression, or response to intervention. By supporting high-quality, interpretable data elements, the FDA is signaling that the funded projects should produce data that can actually be used and trusted by the broader field, including regulators, clinical researchers, and product developers.

A key theme is reducing barriers that commonly block progress in rare diseases: small patient populations, inconsistent outcome measures, lack of validated or promising biomarkers, and limited understanding of disease trajectories. The FOA also explicitly notes an interest in studies that can have a significant and broad impact either on a single rare neurodegenerative disease or across multiple rare neurodegenerative diseases that share similar underlying biology or pathophysiology. That suggests the FDA is receptive to projects that are disease-specific as well as projects that are strategically designed to generate insights or tools that can be translated across related conditions, potentially improving efficiency for multiple development programs.

The "Clinical Trials Optional" designation means applicants are not required to propose a clinical trial to be responsive to the FOA, but they may include clinical trial components if appropriate to the research goals and allowed within the program requirements. In this context, the main intent is not to fund traditional therapeutic efficacy trials, but rather to fund foundational studies that make later therapeutic trials more feasible, interpretable, and regulatorily meaningful by defining endpoints, trajectories, and biomarkers.

In terms of funding scale and competitiveness, the opportunity lists an award ceiling of $2,000,000 and anticipates making 2 awards. While the notice does not specify the exact project period here, the ceiling and small number of expected awards indicate a relatively selective competition aimed at projects with clear justification, strong design, and a high likelihood of producing field-shaping datasets or biomarker insights.

Eligibility is broad and includes many organizational types that typically participate in clinical research and data infrastructure work. Eligible applicants include state, county, and local 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 and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories); for-profit organizations other than small businesses; small businesses; and other entities as further clarified in the full eligibility text. This breadth suggests the FDA is open to applications from academic medical centers, nonprofits and foundations, research institutes, biotechnology-related organizations, and potentially consortia that can recruit and follow rare-disease cohorts and generate robust clinical and biomarker datasets.

Overall, the opportunity is positioned as a regulatory-science-informed investment meant to accelerate rare neurodegenerative disease product development by building the foundational knowledge needed to design better trials, select meaningful endpoints, and interpret treatment effects. The FDA expectation is that funded natural history and biomarker work will generate high-quality data that closes critical gaps, supports shared understanding of disease progression, and ultimately helps de-risk development programs for therapies targeting rare neurodegenerative disorders.

• The Department of Health and Human Services, Food and Drug Administration in the consumer protection, science and technology and other research and development sector is offering a public funding opportunity titled "Natural History and Biomarker Studies of Rare Neurodegenerative Diseases (U01) Clinical Trials Optional" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.103.
• This funding opportunity was created on Feb 27, 2023.
• Applicants must submit their applications by May 04, 2023. (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 $2,000,000.00 in funding.
• The number of recipients for this funding is limited to 2 candidate(s).
• 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 (see text field entitled Additional Information on Eligibility for clarification).

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