The National Institutes of Health (NIH), through the National Institute of Neurological Disorders and Stroke (NINDS), announces a funding opportunity titled "Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders" (PAR-25-327). The program aims to fund research for Investigational New Drug (IND)-enabling studies and preparation for First-in-Human (FIH) trials focusing on gene-based therapies for ultra-rare diseases affecting fewer than 6,000 patients. A milestone-driven cooperative agreement mechanism (U01) will be utilized, supporting projects that demonstrate robust proof of concept data and are poised for clinical trial readiness. Key funding goals include advancing innovative therapies such as oligonucleotides and viral vector-based approaches while facilitating regulatory pathways to expedite patient access to treatments. Eligible applicants include higher education institutions and various nonprofit and for-profit organizations. Applications require detailed project planning, including compliance with Good Manufacturing Practices (GMP) and submission of IND applications. Important deadlines include an application opening date of January 9, 2025, with funding decisions following rigorous peer review based on scientific merit and relevance to program priorities. The opportunity underlines NIH's commitment to supporting groundbreaking research in the field of ultra-rare neurological and neuromuscular disorders.