Ten years ago, an athletic 12-year-old from Affton, Missouri, named Mitchell Herndon began to experience muscle weakness that eventually led to him using a wheelchair. After years of visits to specialists failed to diagnose his neurological symptoms, he enrolled in a National Institutes of Health (NIH) -funded program that studies patients with debilitating mystery diseases. Researchers eventually found an explanation for Mitchell’s condition: a mutated gene that causes certain brain cells to produce an overactive protein that leads to neuron damage.
Mitchell died 3 years ago at age 19. Since then, 14 more people have been identified with the same disease, dubbed Mitchell syndrome, and his family started a foundation that hopes to develop a treatment.
His case is one of hundreds cracked by a highly regarded NIH program called the Undiagnosed Diseases Network (UDN) over the past 9 years. Now, however, funding is winding down for the network — and some including patient advocates, are scrambling to persuade Congress to restore full funding or keep at least parts of it afloat.
The UDN supports teams of clinicians, geneticists, and other experts who study patients with medical cases that have confounded their doctors and specialists. It was designed to sunset 10 years after being established in 2013, and a new NIH program to carry on its work will get less than one-third as much as its current funding. With their NIH support ending in a year, seven of the network’s 12 clinical sites are turning away new patients and focusing on current cases.
“The significant funding cut is a challenge,” says genetic counselor Kimberly LeBlanc, director of the UDN Coordinating Center at Harvard Medical School. But she and others hope federal lawmakers will restore more UDN funding in NIH’s 2023 spending bill, which is working its way through Congress.
“I want to see the UDN sites not only continue but to [also] grow and make even more discoveries and… impacts on the lives of patients and families, ”Michele Herndon, Mitchell’s mother, recently wrote to a staffer for Senator Roy Blunt (R – MO). “We hope it will continue to grow.”
The UDN emerged from an effort launched in 2008 by the NIH Clinical Center in Bethesda, Maryland, to study people with puzzling symptoms using exhaustive clinical workups exome sequencing, a then-new tool that scours a person’s protein-coding DNA for a culprit gene. The program’s success led NIH’s Common Fund, dedicated to new programs, to launch a national network that grew to include the NIH intramural program and 11 medical centers around the country. Funding grew from $ 10 million in 2013 to about $ 30 million for several years, then tapered to an estimated $ 16 million this year.
It is an undisputed success: The network has solved about 30% of nearly 1900 cases so far, finding hundreds of novel disease mutations and nearly 50 new disorders. It has published more than 175 papers and drawn a stream of positive TV and press stories.
Like other Common Fund programs before it, the UDN needed to find a home within NIH’s 27 institutes. The current plan is for the National Institute of Neurological Disorders and Stroke (NINDS) to lead a new data and coordinating center, with four other institutes helping provide an annual $ 5 million budget for 5 years. NIH sees the UDN “evolving into a larger, self-sustained network,” a notice says.
The current sites can apply to join — but the agency plans to directly fund only the intramural site at NIH. In part, that’s because genome sequencing has become a routine part of medicine that is often covered by insurance, an NIH spokesperson notes, although UDN researchers say only some insurers cover it.
The new NINDS coordinating center will fund small research grants, but scientists say this will not be enough to compensate for the network’s existing research resources. Those include model organism screening centers, a metabolomics center, and research at the clinical sites such as RNA sequencing. Without these research components, the UDN would be “less robust,” says clinical geneticist Vandana Shashi, who heads Duke University’s UDN site.
Also troubling to UDN scientists and advocates is the fact that more than 1300 cases remain unsolved, often because scientists need to create an animal model or find another patient to confirm a suspected disease mutation. “Research is still needed to find an answer,” LeBlanc says.
The NIH spokesperson says the agency is “working with Congress on other models to expand [the UDN’s] impact, ”particularly in underserved communities where many patients can not get the basic diagnostic workup required to qualify for the UDN.
Meanwhile, some sites have cobbled together donations, parts of other NIH grants, and other support and expect to reopen in a few months. Others are still figuring out whether they can keep going.
“We hope to continue this work in any way possible, since we are passionate and committed to this mission,” Shashi says.