NINDS launches URGenT: A network to accelerate the development of treatments for ultra-rare neurological diseases

In the United States, rare and ultra-rare diseases are defined as conditions that affect fewer than 200,000 or 6,000 people, respectively. While these numbers may seem small, they add up to a large burden: collectively, nearly 30 million Americans are living with one of the roughly 7,000 known rare or ultra-rare diseases. Furthermore, approximately 45% of rare and ultra-rare diseases are associated with neurological symptoms. Currently, most treatments for rare and ultra-rare diseases target symptoms and rarely address root causes. For people afflicted by these diseases and their families, the current standard of care is simply not enough. Patients, families, and advocacy groups are pushing for progress in precise and early treatments to prevent life-long disability or early mortality. To address these needs, I am delighted to announce the launch of a new NINDS program – the Ultra-rare Gene-based Therapy (URGenT) network, which will support the development of state-of-the-art gene-based therapies for ultra-rare neurological diseases.

Advances in gene therapy technologies now offer promising new possibilities to design precision therapies that target the underlying genetic causes of disease. Many rare and ultra-rare diseases are caused by single-gene variations, making them excellent targets for gene therapies. Additionally, genetic testing has become increasingly more affordable and accessible, allowing for early diagnosis and potential therapeutic intervention before the onset of nervous system abnormalities. The toolkit for genetic intervention has also widely expanded, allowing for the replacement of disease-causing gene variations, or altered expression of beneficial or harmful genes. However, the traditional pathway for developing gene-based treatments is challenging to apply to ultra-rare diseases since their patient populations are small and dispersed, the regulatory pathway for new therapies is still evolving, and funding for ultra-rare diseases is scarce.

The need for a collaborative network approach to developing gene-based therapies for ultra-rare diseases emerged through discussions at a workshop held by NINDS in 2019, on “Next-generation strategies for gene-targeted therapies of central nervous system disorders.” As initially outlined by NINDS Deputy Director Dr. Nina Schor, URGenT aims to develop optimal paths for the development of gene-based therapies for ultra-rare neurological diseases from late-stage pre-clinical development into first-in-human clinical testing. I am excited for the launch of URGenT because it will provide the necessary funding, resources, and structure to connect academia, the non-profit sector, and health care providers. Our hope is that this network of experts will facilitate the standardization and harmonization of best practices for developing gene-based therapies for ultra-rare diseases, which will yield benefits for diseases beyond those that receive direct support through the program.

We recently published an article in Nature Biotechnology discussing URGenT, and I am happy to announce that we now have two new funding opportunities to support this exciting initiative. The first, “Ultra-Rare Gene-based Therapy (URGenT) Network Resource Access,” will provide a framework for investigators to access a network of contract research/medical organizations (CROs/CMOs) and subject matter experts. These groups will support investigators with planning, manufacturing, and some non-clinical therapeutic development resources.

The second funding opportunity, “Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders,” accelerates therapeutic development. More specifically, it is will support studies to enable Investigational New Drug (IND) applications to the Food and Drug Administration (FDA), which are necessary for testing new therapies in people. Importantly, we hope that successful projects will lead to clinical trials for promising therapeutic candidates.

Developing tailored therapies for ultra-rare neurological diseases is a daunting pursuit, yet I am hopeful about the mission and impact of URGenT. I encourage everyone who is eligible to apply for these exciting funding opportunities. The first application deadline for both is December 22, 2021, with future deadlines planned through June 7, 2024.