NIH’s much-vaunted program to solve baffling medical cases is running out of money | Science

Ten years ago, a 12-year-old sportsman from Affton, Missouri named Mitchell Herndon began to experience muscle weakness that eventually led him to use a wheelchair. After years of visits to specialists who failed to diagnose his neurological symptoms, he enrolled in a program funded by the National Institutes of Health (NIH) that studies patients with debilitating mystery diseases. Researchers have finally found an explanation for Mitchell’s condition: a mutated gene that causes certain brain cells to produce an overactive protein that damages neurons.

Mitchell passed away 3 years ago at the age of 19. Since then, 14 other people have been identified with the same disease, dubbed Mitchell’s syndrome, and his family has set up 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 for the network is winding down, and some, including patient advocates, are scrambling to persuade Congress to restore full funding or at least keep some of it afloat.

UDN supports teams of clinicians, geneticists and other experts who study patients whose medical cases have confused their doctors and specialists. It was designed to expire 10 years after its creation in 2013, and a new NIH program to continue its work will receive less than a third of 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 reduction in funding 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 the NIH’s 2023 spending bill, which is making its way through Congress.

“I want to see UDN sites not only continue but [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 of Sen. Roy Blunt (R–MO). “We hope it will continue to develop.”

UDN grew out of a 2008 effort by the NIH Clinical Center in Bethesda, Maryland, to study people with puzzling symptoms using comprehensive exome sequencing clinical workups, a then-new tool that scans a person’s protein-coding DNA for the culprit gene. The success of the program led the NIH Common Fund, dedicated to new programs, to launch a national network that has grown to include the NIH Intramural Program and 11 medical centers across the country. Funding went from $10 million in 2013 to about $30 million for several years, then dropped to about $16 million this year.

It’s an undisputed success: the network has solved about 30% of the nearly 1,900 cases to date, finding hundreds of new disease mutations and nearly 50 new disorders. He has published over 175 articles and attracted a stream of positive articles on television and in the press.

Like other Common Fund programs before it, UDN had to find a seat within the 27 NIH 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 to provide an annual budget of $5 million for 5 years. The NIH sees UDN “evolving into a larger, self-sustaining network,” a notice said.

Current sites can apply for membership, but the agency plans to directly fund only the NIH intramural site. In part, that’s because genome sequencing has become a mainstream part of medicine that’s often covered by insurance, an NIH spokesperson notes, though UDN researchers say only certain insurers do so. cover.

The new NINDS Coordinating Center will fund small research grants, but scientists say this will not be enough to offset the network’s existing research resources. These include model organism screening centers, a metabolomics center and clinical site research such as RNA sequencing. Without these research components, UDN will be “less robust,” says clinical geneticist Vandana Shashi, who directs the UDN site at Duke University.

The fact that more than 1,300 cases remain unsolved, often because scientists need to create an animal model or find another patient to confirm a suspected disease mutation, is also troubling to UDN scientists and advocates. “Research is still needed to find an answer,” says LeBlanc.

The NIH spokesperson said the agency “is working with Congress on other models to expand [the UDN’s] impact,” especially in underserved communities where many patients cannot get the basic diagnostic workup required to qualify for UDN.

Meanwhile, some sites have cobbled together donations, parts of other NIH grants and other support, and plan to reopen in a few months. Others are still wondering if they can continue.

“We hope to continue this work in any way we can because we are passionate and committed to this mission,” Shashi says.

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