Recent successes of therapies aimed at replacing, blocking, or changing the reading of genes—referred to as gene therapy—have made real the prospect of improving outcomes for people with rare diseases. In September 2019, NINDS held a workshop entitled “Next Generation Strategies for Gene-Targeted Therapies of Central Nervous System Disorders” to brainstorm with scientists, pharmaceutical manufacturers, and patient advocates about the best ways of getting these cutting-edge treatments into the hands of doctors and scientists to help improve the lives of patients living with rare diseases.
It is estimated that there are between 5,000 and 8,000 rare diseases, which are defined as diseases that currently affect fewer than 200,000 people in the United States. Collectively, these diseases affect roughly 400 million people worldwide, and one-third of rare diseases involve the nervous system—the brain, spinal cord, nerves, and/or the muscles
In recent years, gene therapies have emerged as a promising way to treat several of these rare diseases. However, there are a few hurdles that still stand in the way.
- The cost of production, validation of safety and effectiveness, and approval by the FDA of these therapies threatens to be prohibitive.
- We still need to determine how to package and deliver genetic or “antisense” blocking material to use for a given disease and patient.
- Determining how to overcome immune (almost like allergic) reactions to the viruses used to deliver genes may prove difficult when so few people would get each virus-gene “drug” and scientists have not yet agreed on what exactly to measure to predict when such reactions are likely to occur.
It became clear to us from our workshop discussion that there were enormous disparities concerning access to the kind of personalized medicine gene therapy could provide to patients with rare diseases. We therefore began planning the Ultra-Rare Gene Therapy (URGenT) network to improve access to these therapies for patients and families with rare diseases and the physicians who care for them. The aims of the URGenT network are as follows:
- Accelerate advancement of genetic discoveries into the clinic;
- Provide resources and expertise not otherwise available to all scientists and doctors;
- Make therapeutic options available to patients with ultra-rare diseases; and
- Eventually create standards and guidelines for the development of gene-based therapies for ultra-rare diseases.
In February 2020, the concept proposal for the URGenT network was approved by the NINDS Advisory Council, and we were on our way!
To be sure, NINDS had been funding research on gene-targeted therapies for rare diseases for many years. In the 2019 funding year, NINDS funded 935 active grants on rare disease research. In the past 5 years, NINDS has awarded 31 new grants focused on gene-based therapy for ultra-rare diseases. This may seem like a low number, but it really highlights challenges we must address, as only a few institutions and communities are today able to support and sustain such research and the challenges it presents. The URGenT network will provide expertise, in-kind services, and funding to scientists and doctors on an application-based competitive basis. Those who have a good idea and a scientific compelling rationale for it will be given resources to bring that idea from the laboratory to the patients it could help. NINDS is excited to introduce the URGenT network in this era of heightened awareness around disparities in access to health and healthcare; the power and challenges of bringing advanced technologies to patients and families; and the need for building efficiencies and synergies through collaboration, and we expect to begin accepting applications from scientists and doctors sometime in 2021. We look forward to partnering with a diverse array of colleagues in using science to ease the burden of those in the rare disease community.