Not actionable. Matt and Cristina Might would like to see those words stricken from medicine’s vernacular.
To parents of children with ill-defined diseases, those words are disempowering, signaling another dead end in the search for a diagnosis and treatment. They’re also misleading, says Matt Might, Ph.D., University of Utah associate professor of computer science and adviser to President Obama’s precision medicine initiative. Because in the absence of actionable knowledge, treatments or cures, “science becomes medicine,” he says.
For millions in the rare disease community, the Mights’ diagnostic odyssey has a familiar beginning. The family had just relocated to Salt Lake when concerns deepened about their 6-month-old son, Bertrand. The couple feared autism, the first of a cascade of disorders—each scarier than the last—to be ruled out over four years of EKGs, CT scans, biopsies and blood draws. “You don’t know why your child is hurting or how to stop it,” recalls Matt. In their case, they didn’t know why Bertrand was having seizures and couldn’t cry tears.
They cried plenty for him, says Cristina Might, M.B.A., who put aside her career plans to care for Bertrand and “stitch together” a team of experts. “I spent my time flying him to Duke, Stanford, Baylor; my full time job was just getting answers.” She scoured the Internet for research and clinical trials, sharing everything she learned on a blog: “It’s difficult feeling so alone, so un-Googleable.”
From physical therapy to a stem cell transplant, they explored all avenues. In 2009, they closed Bertrand’s college account to cover medical expenses. Then in 2012, a breakthrough: Duke University scientists who knew the Mights through their transplant attempt invited them to take part in a study of the use of exome sequencing for diagnosing rare diseases. The study unearthed a mutation in the NGLY1 gene that they suspected was the source of Bertrand’s disorder. Matt describes it as having been “rescued from undiagnosed island.”
‘Reverse Dragnet’
There was comfort in having something to target with experimental therapies. But they needed to confirm this mutation was the culprit, which traditionally entails months of lab work. Instead, the Mights found success with a user-friendly tool—the Internet.
Matt leveraged the social media audience he had amassed through his academic writings and in May, 2012 published a blog post about the “hunt” for his “son’s killer.” He hoped it would act as a “reverse dragnet” to find other patients just like Bertrand.
It worked. The post was seen by millions. Within months the Mights heard from a handful of NGLY1 patients from around the globe, and from researchers who volunteered to test Bertrand’s cells and explore treatments. “Within three months of getting a diagnosis we were trying a compound,” says Matt.
Self-education pointed to a promising supplement. He found it on Amazon and after taking it himself with no adverse effects—“In my house, I am the FDA,” he says—gave it to Bertrand. Within three days, his son cried his first tear. “It was one small tear but an ocean of science for the disorder because it gave us a clue that this is in some way fundamentally impacting the disorder,” Matt says. Months after taking the supplement, which costs 25 cents a day, Bertrand’s seizures stopped. And his medical expenses have dropped from hundreds of thousands of dollars to less than $30,000 a year.
Their newfound cyber support group replaced “the darkness of isolation” with the “comfort and power of community,” Matt says. Also, sharing stories and clinical data sparked threads for scientists to follow, such as an uncanny ability of NGLY1 patients to ward off viruses, which could be instructive for fighting infectious disease. The families started two nonprofits and supported development of an assay and animal models for testing the 30-plus compounds they’ve identified as possible treatments.
From Citizen Scientist to the White House
The Mights are acutely aware that not everyone has their depth of resources, knowledge or connections. “We had means to travel the world, but most families don’t,” says Cristina. “We’re trying to figure out how we can level the playing field because it’s not fair.”
Matt believes their success is replicable and scalable, which is why he accepts many of the near-daily invitations to share what he’s learned with audiences around the world. Patients can drive science and shape it, he says, offering as proof his own trajectory from concerned father to advising the president’s precision medicine initiative, testifying before Congress and collaborating with University of Utah researchers to develop an NGLY1 therapy. The optimism that drives the Mights doesn’t cloud their view of reality. “I’m very proud of the fact that Matt’s trying to make it better not just for our son,” says Cristina. “Bertrand’s not going to benefit from a lot of the work we’re doing now but other families will and already have. That’s the beautiful thing.”
With Bertrand and two younger children, Cristina’s geographical radius is smaller but her influence is no less great. She is a connector of families, doctors and researchers and a mentor. “It helps to know how the game is played,” she says. “There are little ‘cheat codes’ that make a big difference in finding the right specialist or getting seen sooner.” She’s also co-founded an advocacy group, Utah Rare, and is helping to raise money for an “undiagnosed” clinic at the University of Utah, designed to shepherd families through complicated diagnoses.
There remain barriers to building a scientific community that’s truly inclusive of patients—from Institutional Review Board (IRB) restrictions on sharing data to the pay walls barring public access to many scientific journals. But it’s getting better, says Matt. “Institutions that figure out how to harness patient energy will be the ones that leapfrog to the front. Patients will seek those places out.”
Kirsten Stewart is a senior writer for University of Utah Health Sciences