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

The Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders funding opportunity, issued by the National Institute of Neurological Disorders and Stroke, seeks to advance gene-based and transcript-directed therapeutics for ultra-rare neurological and neuromuscular disorders. This funding opportunity supports Investigational New Drug-enabling studies and clinical trial planning for First-in-Human trials. The program aims to accelerate the development of therapies with strong biological rationale and robust proof-of-concept data for diseases affecting 6,000 or fewer individuals in the United States. The funding focuses on various therapeutic approaches, including oligonucleotide-based therapies, viral vector-based strategies, gene-modified cell therapies, genome editing technologies, and small-molecule therapies that target RNA splicing. Applicants must demonstrate significant proof-of-concept data supporting their therapeutic candidate, including in vitro and/or in vivo studies in a relevant disease model. Applicants are expected to have held pre-IND meetings or formal discussions with the Food and Drug Administration to outline regulatory pathways. Projects should include activities such as process development, cGMP manufacturing, IND-enabling toxicology and biodistribution studies, and clinical trial planning. Eligible organizations include higher education institutions, nonprofit organizations, small businesses, for-profit organizations, and local, state, and tribal governments. Non-domestic organizations are not eligible to apply, though foreign components of U.S. organizations may participate. Applications must reflect a milestone-driven approach, outlining key steps and Go/No-Go criteria to ensure the feasibility of IND-enabling studies and clinical trial readiness. Projects must be completed within a three-year timeframe. The URGenT program emphasizes collaborative development through the formation of a Multi-disciplinary Project Team, which includes NIH program staff, external subject matter experts, and the principal investigator's team. Applicants will also have access to NINDS contract resources to support manufacturing, nonclinical toxicology testing, and other development needs. Intellectual property arrangements must be managed by the applicant’s institution, with plans for commercialization outlined as part of the submission. Applications must include preliminary data, pre-IND meeting minutes, intellectual property documentation, and a Target Product Profile describing the intended therapeutic characteristics. The application will be evaluated based on the strength of the biological rationale, rigor of the experimental design, feasibility of the proposed development plan, and the expertise of the research team. Proposals that do not meet eligibility criteria, such as those lacking identified therapeutic candidates or sufficient proof-of-concept data, will be deemed nonresponsive. Applications are accepted multiple times per year, with deadlines in February, June, and October. Letters of intent are encouraged at least 30 days prior to submission. Applications must be submitted through Grants.gov, and applicants must complete all required registrations, including those for SAM.gov and eRA Commons. For questions, applicants are encouraged to consult with NINDS program staff well in advance of submission. The ultimate goal of this funding opportunity is to advance therapies toward clinical trials, providing a pathway for treatment options for individuals with ultra-rare neurological and neuromuscular disorders.