Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders (U01 - Clinical Trial Optional) | PAR 25 327

Opportunity Information: Apply for PAR 25 327

The NIH funding opportunity PAR-25-327 is a cooperative agreement (U01, clinical trial optional) focused on speeding up translation of gene-based and transcript-directed therapies for ultra-rare neurological and neuromuscular disorders. It sits within the Ultra-Rare Gene-Based Therapy (URGenT) network and is specifically aimed at taking a therapy that already looks genuinely promising and pushing it through the remaining preclinical and operational steps needed to reach an Investigational New Drug (IND) application and begin a first-in-human (FIH) clinical study. In practical terms, this is meant for projects that have moved beyond early discovery and now need a structured, milestone-driven path to IND-enabling studies and clinical trial readiness.

The scientific scope centers on gene-based or transcript-directed therapeutic modalities, with examples including oligonucleotide approaches and viral-based gene therapies. The emphasis is on ultra-rare disorders affecting the nervous system or neuromuscular function, where traditional commercial development pathways are often difficult due to small patient populations. To fit the intent of the program, an application should be anchored in a well-supported biological rationale for the target disease and mechanism, and it should already have proof-of-concept (POC) evidence for the proposed therapeutic strategy in a model system that is relevant to the intended patient population. The core expectation is that the proposed work will materially de-risk and advance a defined clinical candidate toward IND submission, rather than exploring broad platform concepts without a clear, near-term candidate and development plan.

Because the mechanism is a cooperative agreement, NIH involvement is typically more active than in a standard research grant, with an expectation of coordinated planning, progress tracking, and alignment with network goals. The opportunity explicitly supports IND-enabling studies and planning activities required for FIH testing, meaning projects should be framed around the kinds of deliverables regulators expect before human dosing (for example, the preclinical evidence package, readiness for manufacturing and quality considerations, and clinical planning). While clinical trials are listed as optional under the U01, the stated program goal is to move projects to the point where a clinical trial can be initiated, so strong applications generally align their timelines and milestones with that end point.

Eligibility is broad across public and private sectors. 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; tribal organizations (other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other organizations. The announcement also calls out additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, regional organizations, eligible federal agencies, tribal governments that are not federally recognized, and U.S. territories or possessions.

Foreign eligibility is constrained. Non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components are allowed when they meet the NIH Grants Policy Statement definition, which generally means a U.S.-based applicant organization can include a justified foreign component in the project when it is necessary for the project and offers special expertise, resources, populations, or other unique capabilities not readily available in the United States.

Administratively, the sponsoring agency is the National Institutes of Health, the opportunity is categorized as discretionary funding, the activity category is health, and the CFDA (Assistance Listing) number provided is 93.853. The opportunity was created on 2024-12-18, and the original closing date listed is 2027-10-08. An award ceiling and expected number of awards are not specified in the provided source text, which usually signals that applicants should consult the full notice for budget guidance, project period expectations, and any institute-specific limits or milestones tied to URGenT network participation.

Overall, this opportunity is best understood as a translational bridge for ultra-rare neuro and neuromuscular gene-based therapy programs that already have convincing early evidence and now need coordinated support to complete IND-enabling work and be ready to launch a first-in-human trial.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders (U01 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853.
• This funding opportunity was created on 2024-12-18.
• Applicants must submit their applications by 2027-10-08.
• 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 PAR 25 327

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