Until recently, having a rare or undiagnosed disease almost invariably meant that a person would have to suffer through a years-long diagnostic odyssey, enduring batteries of expensive tests with little promise of getting an answer. While this fate is still inevitable for some people, expanding access to affordable, comprehensive sequencing has radically changed the prospects for achieving a diagnosis.

This kind of work is happening around the world, but one long-running programme in the United States offers an example of how much impact this approach can have. Launched in 2008 by the US National Institutes of Health, the Undiagnosed Diseases Network (UDN) offers critical diagnostic resources to people and families with ultra-rare or undiagnosed diseases. The programme partners with the Undiagnosed Diseases Network International to expand these resources to patients, physicians, and clinical researchers around the world.

In the US, the network includes nearly 20 clinical sites at academic medical centres, where scientists and clinical researchers work with participants and their families. More than 2,000 participants have been enrolled since the programme began, and nearly 700 have received at least one confirmed or highly likely diagnosis. That’s a success rate better than 30% for some of the most challenging medical cases in the world.

The vast majority of those diagnoses—more than 80%—have been enabled by whole exome or whole genome sequencing, with smaller contributions from directed clinical testing, chromosomal microarrays, karyotyping, and other techniques. The most common clinical symptoms, seen in about 40% of patients, have been neurological.

Perhaps most exciting, the network’s efforts have led to more than 60 newly identified diseases, which may allow for the development of new rare disease diagnostic tests to help other patients suffering from the same previously undiagnosable conditions.

Earlier this year, the Undiagnosed Diseases Network Foundation (UDNF) was launched to help provide non-government financial support to ensure the long-term viability of the network. Lab Insights caught up with Amy Gray, inaugural CEO of the organisation, to learn more.

Why is there a need for this foundation?

AG: The Undiagnosed Diseases Network has been such a remarkable programme; it is one of the most successful that NIH has ever launched. The idea for a patient-led foundation to support the network came from patients, physicians, researchers, and other stakeholders who wanted to ensure the sustainability and growth of this programme whenever NIH funding ends.

We also want to support the undiagnosed and ultra-rare disease communities, who may not have many other resources to turn to. I have spent my career in nonprofit healthcare philanthropy in a variety of rare disease areas and there was never a single organisation for people who do not have a definitive diagnosis. There is such a big need for that and this foundation is here to meet that need.

How will having access to a community like this make a difference for patients?

AG: Without this foundation, families are left to navigate this difficult journey themselves. When we convened a group of stakeholders to discuss plans for the foundation, it was very clear that families want a place where they and others can turn for a community of support so no one has to go on this journey alone.

One of the first programmes we’ll be launching is a patient and family navigation programme that will help guide people along the path to determining a diagnosis and then getting access to treatments and more. We know that when you get a group of parents and families together, there’s no stopping them. We really want to enable that kind of community.

How can diagnostic tools be helpful to this community?

AG: A big part of what we’re focused on is access and equity when it comes to diagnostic technologies, and right now we are particularly interested in rapid whole genome sequencing. When diagnostic companies can partner with community organisations, that will be really critical for solving undiagnosed and ultra-rare disease cases. We are hoping to establish partnerships with diagnostic companies and to help educate the healthcare community about new diagnostic options as they come out.