By Allison Proffitt
September 20, 2016 | About a year ago, Boston Children’s Hospital launched its second CLARITY challenge. CLARITY Undiagnosed focused on six patient families searching for a diagnosis. Alongside the challenge, a documentary is being filmed, driven by Katia Moritz, a Florida psychologist who is dealing with her own undiagnosed disease. And last month another piece of the puzzle fell into place: the UnDx Consortium met in San Diego to try to put context around these diseases.
Doug Jamison, co-organizer of the UnDx Consortium, and Moritz launched the idea last fall. “Katia and I were talking, and I was getting an update on both the Undiagnosed Medical Refugees film she’s doing, and… the CLARITY project… and my question to her was, wouldn’t it be really interesting if we could provide contextual information around the genomic information that was being done CLARITY Undiagnosed?” Jamison told Diagnostics World.
The patients who were part of the CLARITY challenge had extensive medical histories and were now adding sequencing to their charts. “But you’re not your genes alone,” Jamison points out. “Your genes reside in your cells and all the context is around the cell.”
The idea took off.
Over the first half of 2016, Jamison gathered five companies working on metabolomics, epigenetics, microbiome analysis, stem cells and regenerative medicine, and chromosomal rearrangements. “We brought those five groups together to sample the same patient cohort as CLARITY Undiagnosed and see what we can find,” he explained.
Jamison says he picked the companies that he was familiar with and were available. All of the companies donated their time and services to the Consortium.
Genome Profiling of Wilmington, DE, provided epigenetic analysis; the lab of Rob Knight and the American Gut Project at the University of California San Diego (UCSD), provided microbiome analysis; KromaTiD, of Fort Collins, CO, provided a chromosomal imaging platform for the detection of chromosomal rearrangements; Metabolon, of Durham, NC, provided metabolomic analysis; and ORIG3N of Boston, MA, providing both the sample collection and stem cell analysis.
Each company evaluated the CLARITY Undiagnosed patients and presented their findings at the Consortium in San Diego on August 15.
Jamison couldn’t reveal any personal health information, of course, but he did say that the UnDx Consortium brought new information to the table for most patients, and some patients had possible diagnoses ruled out. Some of the patients had perturbed microbiomes. One patient had very high levels of ammonia highlighting a particular metabolic pathway. Many were hypomethylated. One patient showed significant chromosomal rearrangements, prompting resequencing.
“Now you actually have these 5-6 different technologies collaborating. They’re going back to the sequencing to look at it, to really begin to answer disease issues for these patients,” Jamison said.
This view of personalized medicine might reshape how we think of diagnostics.
“’Diagnosing’ might be the wrong term. We may not be ‘diagnosing’; we may be understanding each person’s individual disease and treating it for them,” Jamison said. “Ultimately what we want to provide is information and actions that they can take to improve their current status.”
Proof of Concept
Jamison emphasizes that the UnDx Consortium was a proof of concept exercise to bring contextual information to bear on genomics and patient medical records.
“This is the first time these technologies have come together on real patients to try to find new hypotheses and work with them. I’d definitely call them more science and technology and less medicine.”
Jamison intends for the UnDx Consortium to be an annual event. He hopes to add more technologies next year—he mentions neurology and imaging, transcriptomics, proteomics.
Scaling efforts like this will certainly be a challenge, Jamison agrees. The Consortium this year included two and a half hours of companies presenting their results, which then prompted collaborative conversations among all of the stakeholders. Collaborating companies shared their findings with the clinicians in attendance (two primary care doctors for CLARITY Undiagnosed patients, as well as several physicians associate with the CLARITY projects), and together everyone talked about next steps. Results were forwarded on to the doctors not in attendance.
The scale question really hinges on how to collect samples, deliver results, and communicate those results in a way clinicians can use, Jamison said. [There’s still a] gap between what we can see from the technology and how we provide actionable information to the clinician... I think that gap will be there for a while.”
Jamison believes there are roles for other groups—large research hospitals and patient advocates—in addressing scale.
“We’re on the front end,” he said, “looking at these new technologies and hopefully providing technologies and solutions that give physicians ways to understand people’s disease, and hopefully take action on it.”