Parental Might Continued from Page 3 Because such mutations are rare, and the symptoms span many diseases, afflicted children typically go undiagnosed. Their pediatricians are baffled, and their parents often feel lost and desperate. Bertrand Might was a somber infant whose erratic movements hinted at neurological damage. A series of tests ruled out a wide spectrum of known disorders, and his condition worsened. Matthew Might, Ph.D., and Cristina Might were determined to find the cause of their son’s illness. “It was up to us to figure out what was wrong with Bertrand, and we began a long diagnostic odyssey,” said Matthew, who teaches computer science at the University of Utah.
The Might family with Dr. Hudson Freeze during a visit to the Sanford Children’s Health Research Center in early 2013.
“We had to become the experts on our son’s disease,” explained Cristina. Their research led them to a Duke University team that sequenced Bertrand’s exome, a part of the genome where mutations are especially destructive. The Duke team discovered a genetic aberration: each parent had a different mutation in the same NGLY1 gene, and Bertrand had inherited both. Duke’s scientists didn’t know if this had occurred in any other child, but they knew who would. “They told us, ‘Go to Hudson Freeze, he’s a world leader in glycobiology,’ ” Matthew recalled. “My mother is a close friend of [Institute trustee] Jeanne Herberger, and Jeanne also recommended him. Hud was the first person to tell us that there were other patients out there with the same rare disorder.” “We found a kindred spirit in Hud,” said Cristina. “We saw at once that his life’s mission is not just to make scientific
4
PORTAL | www.sanfordburnham.org
discoveries, but to find cures. And he approached Bertrand as a whole person and not just a collection of symptoms.”
A New Model of Collaboration On March 20, the journal Genetics in Medicine published an unusual commentary about a CDG syndrome caused by NGLY1 mutations. Its title is “The shifting model in clinical diagnostics: how next-generation sequencing and families are altering the way rare diseases are discovered, studied, and treated.” Its co-authors are Matthew Might and Matt Wilsey, whose little girl has the same disease as Bertrand. The two fathers, who now know eight other families with NGLY1-impaired children, called for “a new model for clinicians and researchers” in which “families, patients, and scientists work jointly to […] enhance collaboration methods and support research toward understanding and treatment.” The Mights credit Freeze as the architect of the new model. “This has been revolutionary,” said Cristina, “and it wouldn’t have been possible without Hud.” The couple is also grateful to Freeze for the revelation that, using invitro fertilization technology, they could have more children without running the risk of another NGLY1 mutation. Cristina, who is expecting her third child in June, said, “Thanks to Hud, we can have a family!” Freeze is teaming up with NGLY1 families to accelerate the development of a new therapy from Edison Pharmaceuticals. The National Institutes of Health is participating in clinical trials, and the Food and Drug Administration is monitoring progress. At Sanford-Burnham’s Sanford Children’s Health Research Center, Freeze’s laboratory, which he expanded with support from the Bertrand Might Research Fund established by the family, is searching for other novel CDG therapies. Across the hall, his office is filled with photographs of CDG children who have won his heart. “Each of these children has been blessed with extraordinary parents,” he said, “and it has been my privilege to work with them.”