NIH Reddit “Ask Me Anything” on Rare Diseases

On Feb. 23, 2021, NIH Director Francis S. Collins, M.D., Ph.D., NCATS Director Christopher P. Austin, M.D., and NCATS Office of Rare Diseases Research Director, Anne R. Pariser, M.D., hosted a Reddit “Ask Me Anything” (AMA) on rare diseases research and gene-based approaches to developing therapies. NIH leaders answered 23 questions about topics, such as gene therapy and gene editing, COVID-19 and rare diseases, treatment development and research support, data sharing, and approaches for translating basic research into the clinic. Read some highlights from the AMA below or see the full conversation on Reddit.

Francis Collins

From Lovememychem

Hi, thank you so much for doing this! What do you see as the biggest barriers to developing therapies for these diseases? As a researcher in the basic sciences, my experience has been that there seems to be a considerable amount of applicable research ongoing even for rare diseases in the academic/preclinical world, but that these have not been pursued for development as therapy. Is this a sentiment you would classify as more broadly true, and if so, what are some of the policy steps that you feel can be taken to improve the situation! Again, thanks so much for doing this!

From NIHGov (Francis Collins)

Much has been written about the so-called “Valley of Death.” Basic science discoveries can lead to fundamental understandings of the causes of disease, but translating that into clinical benefit is a long and difficult journey. For rare diseases where the commercial benefits of a successful therapy may be insufficient to inspire private sector interest, good ideas about therapy may simply not get pursued. NIH is intensely interested in developing ways to cross this valley. One way is for NIH-supported researchers to push the research agenda further along--essentially de-risking a project which may then be appealing to a private sector partner. This is a lot of what the National Center for Advancing Translational Sciences (NCATS) does. NIH can also work with Food and Drug Administration (FDA) to identify ways to facilitate clinical developments that can utilize a template which has already been approved, so that every project doesn’t have to start from square one. We are doing that right now for gene therapy.

Read more about basic science research at NIH:

From StringofLights

How do biases and inequities in healthcare affect the rare disease community in particular? For example, there are issues around access to treatments, but there are also biases that may lead to a delayed or incorrect diagnosis. What has been done to address this? Does the NIH have a role in overcoming these issues? Thank you!

From NIHGov (Francis Collins)

It is unfortunately true that our healthcare system is not free of bias. Rare diseases are no exception. Clearly in the United States, there are health inequities that affect certain populations’ access to healthcare. In addition, rare diseases may encounter a version of bias from providers who are simply unfamiliar with the particular condition and are therefore unprepared to offer the optimal clinical recommendations. NIH seeks to make all of its information on rare diseases accessible to patients and providers. NIH also has a major program in health disparities that aims to identify factors that contribute to bias and to test interventions to try to address those inequities. Our most important partners in addressing these problems are patients and their families, so it is a really good thing that the rare disease community is so active in this space.

Christopher Austin

From Adventurous-Cat-8736

Thanks for doing this AMA! Given the problems inherent in translating results from one species to another and the ethical concerns with animal research, what is NIH doing to advance non-animal research into rare diseases?

From NIHGov (Christopher Austin)

Several NIH Institutes and other government agencies have been working to advance non-animal research and animal alternatives for many years; see for example

NCATS has been at the forefront of this work, both in its Tox21 collaboration with NIEHS/NTP, EPA and FDA and in its Tissue Chip for Drug Screening program, which has developed many human cell-based microfluidic bioreactors to mimic human responses to drugs and toxicants, and to model rare diseases and responses to therapeutics.

From Batcheffect

Thank you for hosting this AMA! No field depends more on equitable data sharing than rare diseases, but neither academic researchers nor private institutions (companies) have much incentive to do so. In fact, the opposite is generally true, since keeping data access exclusive ensures a competitive advantage. What can NIH/government do to further promote (enforce?) data sharing by academic and private institutions?

From NIHGov (Christopher Austin)

Data sharing is critical to all science, and as such NIH has recently announced an important – and more demanding – policy on sharing of data from NIH-supported is another very important required data-sharing program. Complete, open and prompt sharing of data in an interpretable fashion is particularly critical for NCATS, because translational science is a fundamentally integrative discipline, deriving general insights from the aggregation of many individual translational research efforts. But as with so many other issues in translational science, the methods, standards and operational best practices required to efficiently produce translationally useful new insights from the aggregated data that facile sharing allows have yet to be developed and demonstrated, and are major areas of NCATS innovation. Our open informatics work in drug development (e.g., OpenData Portal) and rare diseases (e.g., GARD), the NCATS-coordinated Rare Diseases Clinical Research Network (RDCRN) Data Management and Coordinating Center, and the unprecedented National COVID Cohort Collaborative program are all examples of NCATS data sharing and dissemination initiatives that are accelerating translational discovery. Watch for my February Director’s Message, which will be posted in the next few days, on just this topic of data sharing!

Anne Pariser

From StringofLights

Thank you for doing an AMA! How are you all doing today? Has the internet changed how the rare disease community organizes and generates support? Do you think this has had any impact on the development of treatments? Thank you!

From NIHGov (Anne Pariser)

The internet has opened many doors for rare disease community organizations including: 1. Bringing people together from around the world - it can lessen the isolation that many individuals with rare diseases and their families experience; 2. It provides the ability to share vetted information and best practices; 3. It gives patients and families a voice - they are able to share their experiences with a broad audience, thereby educating people about the rare disease experience; 4. It gives the groups the opportunity to address inaccurate information; 5. It provides the ability to help bring patients together to assist in recruitment efforts for clinical trials.

From Stoopkid4Ever

Hi! First I want to say thank you for doing this! I am signed up for Rare Across America and am attending rare disease day at NIH, so this is a fun bonus! I have idiopathic hypersomnia and there are currently no FDA approved medications for it. What do you think the answer is to advancing clinical research to understand disease and help get them under control? What can we as patients do to help this along? I am part of the CoRDS registry and have participated in every clinical research trial that has come my way, but I'm interested to know if there is more I could be doing. Thank you again!

From NIHGov (Anne Pariser)

I am sorry to hear of your diagnosis with idiopathic hypersomnia (IH), which is a chronic disorder that results in daytime sleepiness, unrefreshing sleep and difficulty awakening, among other symptoms.

A first step for many rare diseases is to better understand the disease course through natural history studies (NHS) and registries, as you are doing.

For patient groups interested in starting and conducting good quality registries and NHS, additional resources are available through NCATS’ RaDaR program.

Another option is to find a patient organization for your disorder, or start a foundation or patient group if one doesn’t exist. Patient advocacy groups (PAGs) or foundations can help you to find and work with other patients and advocates to fully understand the disease, and to work together toward research and care.

The NCATS Toolkit for Patient-Focused Therapy Development (Toolkit) provides a resource that describes the process for starting a patient group. Joining together with other patients to start to develop a research agenda can help to develop a priority list for next steps in a disease.

Some other suggestions:

  • Explore the NCATS Toolkit for more information on the research process and how you can start or support research on your condition.
  • Work with larger rare disease organizations to bring attention to rare diseases, and to take part in educational programs to empower patients.
  • Meet with the researchers conducting clinical research trials. Ask the researchers how you can contribute to research, such as helping to inform the patient community about ongoing research and research needs, and meeting the research team to help them understand your disease, among others.
  • Consider working with researchers and clinicians to hold a scientific meeting to help you develop or organize a scientific agenda.
    • NCATS and other Institutes/Centers (ICs) at NIH help support scientific conferences through grants. Please see NCATS’ conference grants page for more information.
  • The primary NIH IC that works on idiopathic hypersomnia is the National Institute of Neurological Disorders and Stroke (NINDS). Please see their information page for more resources and information