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

November 19, 2021 by


This funding opportunity announcement (FOA) is part of the NINDS Ultra-Rare Gene-based Therapy (URGenT) network. The mission of URGenT is to support and facilitate the development of gene-based or transcript-directed therapeutic agents with compelling proof-of-concept (POC) data towards First-in-Human (FIH) clinical trials for individuals suffering from severely debilitating or life-threatening ultra-rare neurological diseases. Specifically, this FOA will support projects ready to complete Investigational New Drug (IND)-enabling studies and initiate clinical trial planning activities. Successful projects ending with an IND cleared by FDA will be eligible to apply for funding to conduct a FIH clinical trial supported by URGenT network resources.

Applicants must have identified and characterized a clinical therapeutic candidate as supported by robust POC data for the intended therapeutic approach and specific disease. The objective of this program is to support activities, such as IND-enabling safety/toxicology studies, pharmacodynamic and pharmacokinetic (PK/PD) studies, to support initial dosing in humans, development of a clinical protocol, clinical end-point assay development, assembly of a research IND application, and clinical trial planning and preparedness activities. This is a milestone-driven cooperative agreement program involving participation of NIH program staff and external subject matter experts (SMEs) in the development of the project plan and monitoring of research progress.


In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people in the United States, based on the definition created by Congress in the Orphan Drug Act of 1983 and adopted by the FDA. Ultra-rare diseases affect substantially fewer people, less than or equal to 6,000; in the U.S., this equates to as few or fewer than one in 50,000 people. Approximately 95% of rare diseases, including ultra-rare diseases, have no FDA-approved therapeutic available and an estimated 80% of rare diseases have an identified genetic origin. These rare diseases are often due to pathogenic variants in a single gene that alter gene product function. Many rare and ultra-rare diseases are caused by different pathogenic variants, some of which may be unique to a single individual or to a very small number of individuals. Cumulatively, these diseases represent a large unmet medical need as there are few available effective treatments and limited commercial incentive for therapeutic development.

The NINDS Ultra-Rare Gene-based Therapy (URGenT) network addresses challenges within ultra-rare disease communities by facilitating and supporting the development of tailored therapeutic interventions using established precision medicine platforms for the treatment of individuals diagnosed with a debilitating and often fatal, ultra-rare neurological and/or neuromuscular disease. Due to the urgency of these individuals’ conditions, rapid intervention in the clinical course of disease is critical. Therefore, the selection of a viable therapeutic approach will require the ability to customize the design, testing, and delivery of these interventions.

URGenT is poised to leverage nonclinical and manufacturing data from one project to another to enable the continuous reassessment of best development practices and clinical outcomes data. This would make a platform approach to therapeutic development more accessible to ultra-rare disease communities and applicable to a broader range of diseases. In addition, this approach aims to facilitate regulatory harmonization when possible and bring therapeutic interventions to individuals sooner.

The design of early-phase clinical trials for gene-based or transcript-directed therapies for ultra-rare patient populations often differs from the design of clinical trials for other types of therapies and relies upon unique collaborations to be successful. Successful completion of the funded project is expected to lead into a clinical trial, which will be supported by mechanisms targeted to URGenT U01 award recipients through limited competition.

Key Dates:

Open Date (Earliest Submission Date): November 22, 2021
Letter of Intent Due Date(s): 30 days prior to the application due date.
First realistic application due date: February 9, 2022

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Filed Under: Funding Opportunities