Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders (U01 - Clinical Trial Optional) | PAR 22 030

Opportunity Information: Apply for PAR 22 030

Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders (PAR-22-030) is an NIH cooperative agreement (U01) opportunity designed to push ultra-rare disease therapeutic programs past the preclinical-to-clinical bottleneck. It sits within the Ultra-Rare Gene-Based Therapy (URGenT) network and focuses on practical, execution-oriented work needed to get a gene-based or transcript-directed therapy ready for an Investigational New Drug (IND) application and to prepare for, and potentially begin, a first-in-human (FIH) clinical study. The FOA is explicitly aimed at therapies such as oligonucleotide-based approaches (for example, antisense oligonucleotides or other RNA-targeting modalities) and viral-based gene therapies, with the target indications limited to ultra-rare neurological and neuromuscular disorders.

The central purpose is acceleration: applicants are expected to already have a promising clinical candidate concept with a strong biological rationale and proof-of-concept (POC) evidence showing the approach works in a model system that is relevant to a defined patient population. In other words, this is not meant for very early discovery or target hunting. It is meant for teams that can credibly argue they have an approach worth advancing and now need support for the IND-enabling package and the detailed planning that makes an initial clinical trial feasible. Because the mechanism is a cooperative agreement, NIH involvement is typically more active than in a standard research grant, with substantial programmatic input, milestone-driven management, and alignment with network resources and expectations.

Projects supported under this FOA generally fit into two connected tracks of work: (1) IND-enabling studies and (2) planning activities for FIH clinical testing. IND-enabling studies commonly include the types of experiments and documentation regulators expect before human dosing, such as key pharmacology, biodistribution, toxicology, dose and route justification, and chemistry, manufacturing, and controls (CMC) planning appropriate to the modality (for instance, AAV vector production and release testing plans for viral gene therapy, or synthesis and formulation considerations for oligonucleotides). Planning activities for FIH testing typically include assembling the clinical development roadmap, thinking through patient identification and recruitment in extremely small populations, selecting clinically meaningful endpoints, developing a feasible protocol outline, and establishing operational readiness elements that can make or break a trial in an ultra-rare setting. The FOA is “Clinical Trial Optional,” meaning applicants may propose clinical trial activities if appropriate, but the primary emphasis is on getting to the point where a trial can responsibly begin, anchored by an IND submission and credible trial initiation planning.

The opportunity is open to a broad range of applicant types across government, academia, nonprofits, and industry. Eligible applicants include state, county, city/township, and special district governments; independent school districts; public and state-controlled and private institutions of higher education; federally recognized Native American tribal governments; public housing authorities/Indian housing authorities; Native American tribal organizations that are not federally recognized; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those categories as listed); for-profit organizations other than small businesses; small businesses; and other entities. The FOA also highlights additional eligible applicant categories 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, Indian/Native American tribal governments that are not federally recognized, and U.S. territories or possessions.

There are important geographic eligibility limits. Non-domestic (non-U.S.) entities and non-domestic foreign institutions are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible to apply. However, foreign components are allowed as defined by the NIH Grants Policy Statement, which typically means a U.S. applicant organization may include certain foreign activities or collaborations when they are well-justified and meet NIH policy requirements, even though the prime applicant must be domestic.

From a logistics standpoint, the sponsoring agency is the National Institutes of Health, the opportunity category is discretionary, and the activity category is health (CFDA 93.853). The funding instrument is a cooperative agreement (U01). The original closing date listed is 2024-10-11. The public summary does not specify an award ceiling or the number of expected awards, so applicants would need to consult the full FOA text and any associated NIH notices for budget expectations, project period limits, and any milestone or go/no-go structure that often accompanies translational cooperative agreements.

Overall, this FOA is geared toward teams working on ultra-rare neurological or neuromuscular disorders who have already cleared the early proof-of-concept hurdle and now need focused support to complete the regulatory-enabling work, tighten the translational package, and map out the first clinical steps. The practical signal to applicants is that proposals should read like a credible development plan with a defined candidate, a specific patient population, and a clear path to IND and FIH readiness, rather than a broad exploratory research program.

• 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 2021-11-09.
• Applicants must submit their applications by 2024-10-11. (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.

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