Dr. Eric Topol hopes study will shed light on ‘Sudden Unexplained Death’
Researchers at Scripps Translational Science Institute (STSI) have launched a clinical trial aimed at cracking one of the toughest mysteries in forensic science — sudden unexplained death syndrome.
The institute has teamed with San Diego County Medical Examiner, Jonathan Lucas, M.D., to sequence the genomes of adults, children and infants in the region whose death (most likely from heart failure) can’t be explained using traditional medical investigative methods.
A dozen or more of these deaths occur annually in San Diego County, according to the medical examiner.
While large-scale DNA sequencing is increasingly being used to identify cancers and other diseases, and to guide therapies, medical examiners have rarely employed gene sequencing in their investigations.
Through a molecular autopsy study being conducted by STSI, researchers hope to identify genes associated with sudden unexplained death and discover previously unrecognized genetic mechanisms for these types of cases. The findings will be used to develop preventative screening programs and potentially life-saving interventions for relatives of study participants and others with the same DNA signature.
Findings could help save lives
“Using state-of-the-art DNA sequencing and powerful analytic tools, we can, for the first time, determine the root cause of sudden unexpected death in many families,” said STSI Director Eric Topol, M.D., who is also chief academic officer of Scripps Health. “This is something that nobody’s really paid significant attention to using sequencing. We’ve already enrolled five families in just over a month (including two with infant deaths).”
One of the study’s first participants was Jason Lappies, 31, of San Diego, who died June 26, 2014. Lappies’ roommate found his body on the couch of their apartment a few hours after Lappies laid down to watch a World Cup soccer match.
“He was very active and very healthy,” his mother, Mary Lappies, said. “He didn’t show any signs of being sick or not feeling good. It came with absolutely no warning.”
Jason left behind friends across the globe, partly from the time he spent in South Korea teaching English to children, his mother said. “His Facebook profile included the phrase ‘No stoppin’ curiosity,’ which perfectly described the way he lived. … By participating in the molecular autopsy study, Jason’s gift for helping others can live on.”
In almost each instance of sudden unexplained death, family members are left wondering if their relative’s passing was a harbinger of some potential threat to them, said Lucas.
“If genetic sequencing and careful analysis of DNA data can help establish a cause in some of these cases, that could answer important questions for surviving family members and provide a sense of closure from a painful loss,” he said.
Study participants must be younger than age 45, and not have any history of excessive drug use, alcohol abuse, morbid obesity, heart disease or any other serious medical conditions. Potential participants are initially identified by the medical examiner’s staff and then reviewed by the STSI research team. Once the family or other next of kin gives consent, and the participant is accepted into the study, blood and heart muscle samples are collected for analysis. Researchers also plan to sequence the DNA of participant parents or other biological family members for comparison.
Researchers hope to enroll as many as 100 primary study participants. They also are exploring the possibility of expanding the project to other county medical examiner departments in California and other regions of the country.
“(These deaths) aren’t that common and so the more data that we have on families, the more confident we’ll be reporting back to families and making important discoveries about what drives this, so eventually we can not only demystify it, but prevent it,” Topol said. “It’s the old story about the power of numbers. We hope that in the next couple years we’ll have every medical examiner (in the country onboard).”
Topol said one of the leading causes of sudden unexplained death is thought to be a defect in the cardiac ion channels, or pore-forming membrane proteins whose functions include controlling electrical signals. “Electrical mal-circuitry is certainly one of the key incriminating causes,” Topol said.
For more information about the Molecular Autopsy Study, visit clinicaltrials.gov