Baylor Joins NIH Undiagnosed Diseases Network
Eager to help patients and families who struggle for years without a diagnosis, the National Institutes for Health (NIH) has created the Undiagnosed Diseases Network to help provide patients with the answers they have been desperately searching for.
As part of an interdisciplinary approach, the NIH has selected six clinical research institutions from across the country to work together, combining resources and expertise to advance medical knowledge for these rare diseases.
Widely recognized for their advancements in genetics and genomics, Baylor College of Medicine has been selected to be a part of the program and was awarded a $7.3 million dollar grant to support their clinical site.
For the past six years the NIH has been developing the pilot program for the Undiagnosed Disease Network. The intramural program began at the NIH headquarters in Bethesda, Maryland, and took advantage of the clinical research resources available there. Since its inception, the program has evaluated people from all over the U.S. and has been successfully able to diagnose many of the participants.
Soon after the pilot program started, the NIH received an overwhelming response from physician referrals and patients who wanted to be evaluated. Many of the patients who applied were admitted and put through rigorous research studies and testing for evaluation. Using their vast resources in genomics, the NIH provided specialized testing that, for many of these patients, was not readily accessible elsewhere.
As more diagnoses continued to be made, the NIH was able to make several discoveries of new diseases, and in some cases, they were even able to determine better treatment strategies for the troublesome diseases.
The program spurred a tremendous amount of new knowledge and the NIH recognized that if it wanted the program to expand, it needed to collaborate with other top clinical research institutions.
“The NIH really wanted to take advantage of the enormous national resources to try to make discoveries and diagnosis in patients who have rare and unusual diseases which has been problematic in the health care system,” said Brendan Lee, M.D., Ph.D., the principal investigator for the Baylor extension site of the Undiagnosed Disease Network, Interim Chair of Molecular and Human Genetics, and founder and director of the Skeletal Dysplasia Clinic at Texas Children’s Hospital. “We (Baylor) have had a four decade history of leading in genetics and genomics in discovering new genes exactly aligned with the mission of this program.”
When the NIH announced its plans Baylor, and its hospital affiliate Texas Children’s, were determined to join forces and become a part of the program. Recognizing that its location in the Texas Medical Center could be a huge strength, they made sure to put that forward in the application process.
“We at Baylor have been very lucky,” said Lee. “I think what distinguished our application is a combination of the history of discovery we’ve had in genetics and genomics, the support and collaboration with the other departments at Baylor, and more broadly, the other institutions of the Texas Medical Center. “
“The Texas Medical Center has a wealth of expertise and I think there has been a long history of collaboration between institutions,” said Lee. “Potentially being able to tap into expertise at the investigator level has been a well established tradition and certainly adds to our strengths, because when you put an application like this forward it must showcase what we do well. But when we are dealing with undiagnosed disease, having the potential to tap into the broad scientific and medical expertise locally is an enormous strength. Our ability to reach other colleagues in the Texas Medical Center has added real value when we think about the problems that we will encounter in this program.”
In terms of medical genetics, Baylor has proven strength in skeletal biology, cardiovascular biology, neurobiology and metabolic diseases for patients of all ages. Now, as a part of this program, Baylor will expand its focus to all organ areas, and at the same time lend its specialized expertise to other members of the network who may encounter struggles in their evaluation. As one
of the core features of the program, all of the institutions in the network will take an interdisciplinary approach in evaluating patients.
“One of the mechanisms of this program is that if there is a patient with an unusual presentation who may benefit from our expertise, there will be collaboration between sites,” said Lee. “It’s a collaborative network. It may be that other sites may do the initial evaluation, and they say ‘Hey there are some unusual skeletal findings. The investigators at Baylor are really good at this. Let’s communicate and see if we can together identify the basis of the skeletal disease.’ It truly is a network; it’s not separate sites. At some level you’re actually leveraging the expertise broadly of all of these institutions.”
Of the six joining medical institutions, Baylor is the only site located in the South. Although patient evaluations have not yet begun, Baylor is already building a long list of patients from all over the region who want to participate in the program.
“We’ve got quite a big catchment area right now,” said Lee. “Even without the program being formally rolled out, we already have had many inquires and we’ve been keeping a list to try and start responding to all of the patients out there once the program is activated.”
The network plans to begin its outreach with a centralized web portal that can be accessed by physicians and patients across the country. Referrals will be reported to the program, and
in a regional fashion, institutions will then screen candidates to determine their issues and evaluate whether the work that has already been done on the patient was appropriate.
“At the end of the day, the initial decision of who gets picked will be based on if we can, given our abilities and resources, make an impact on that patient’s diagnosis,” said Lee.
“There are many patients who may have already had a complete work up. In that situation, we may not really be able to add very much and it would be a waste of their time and resources to bring those individuals here. We’ll focus on the ones where we think, based on what’s been done already, we can provide added value on the clinical research front.”
In cases where members of the network feel more work or evaluation should be done, and there is a possibility of identifying a diagnosable cause, patients will be invited to the nearest clinical research site for further study. Examples of resources that may be used in this program include imaging, physical examinations, and collections of bio specimens, as well as sequencing of the patient’s genome.
“A big part of this program will be sequencing of the patient’s whole genome, as well as studying other aspects of their genetic architecture, like doing family studies,” said Lee. “All of that information will then be collected and integrated by the team of experts in all different areas—pediatrics, medicine, neurology, genetics, and others—so we can determine what the most likely diagnoses are. That report will then be returned back to the patient, and in cases where there is actually a new discovery, we will then report that to the public.”
Lee says that the goals of the program are two-fold. First, the network wants to help patients and their families determine the cause of their illness. Secondly, the network hopes that by doing extensive research within a rigorous clinical research program, new discoveries will be made that will broadly impact the world of medicine.
“We all are focused on helping the patient, but the patient also helps us and helps medicine broadly,” said Lee. “One of the features of undiagnosed disease is that often times, they point to new experiments in nature. When something goes wrong it causes a previously unrecognized disease. By identifying the cause, we will identify ‘new signposts’ of how things can go wrong in our bodies. By focusing on undiagnosed and difficult to diagnose disease, we may actually highlight something that no one has previously observed. These types of discoveries are the ones that can transform medicine and give us a more refined, higher resolution picture of the human body.”