Houston Chronicle — As a young neurosurgeon, Dr. Dong Kim noticed a pattern in patients who'd suffered brain aneurysms: About one in four would report a family history of the condition, which can lead to sudden bleeding, stroke and death.
"Oh, here we go again," Kim remembers a patient's family member saying. "Another brain aneurysm."
The observation triggered something in him. Maybe it was sympathy or curiosity — or perhaps something more personal. Whatever the reason, Kim became obsessed with the question: Is there a specific genetic trigger causing brain aneurysms, which kill some 12,000 people in the U.S. each year?
After nearly two decades hunting for an answer, it now seems he has one.
Kim, the director of the Memorial Hermann Mischer Neuroscience Institute and chair of neurosurgery at UTHealth's McGovern Medical School, led a team of researchers that found a genetic mutation that seems to cause brain aneurysms. The research team, which included Harvard University scientists, published their findings last month in Stroke, a journal of The American Heart Association.
The implications are significant: With the discovery, researchers can begin searching for other genes connected to aneurysms and someday possibly develop a genetic test to identify and treat patients most at risk, saving lives.
"It's been a long time coming," said Kim, who first received a National Institutes of Health grant 16 years ago to begin studying the question in partnership with a geneticist.
The early years were laborious. Their search for a specific gene was a bit like blindly "digging for gold," Kim said: "You don't know when you're going to hit it." Then, about a decade ago, while working at Harvard, he found what seemed like a big, neon sign saying, "Dig here."
He'd been treating a woman from Maine with a brain aneurysm and soon learned that she was the ninth person in her family to have one. Her daughter suffered an aneurysm at 12. Her mother had died of one. This, he knew, was a rare opportunity.
"Part of the problem, because this is a deadly disease, a lot of times there was this extensive family history but no way to study it," Kim said.
He set out to collect samples from as many members of the Maine family as possible — those who'd had aneurysms and those who hadn't — and search for genetic patterns. At one point, Kim even traveled to the small town where they lived and threw a family reunion to get more extended family members enrolled.
In the end, he and his fellow researchers studied 30 of the woman's relatives, ultimately honing in on a little-understood gene, known as THSD1. The protein coding gene appeared to be mutated in each of the family members who'd suffered an aneurysm and functioning normally in all of those who hadn't.
The research has taken off from there. In the latest study, the researchers confirmed the finding in an examination of 500 patients, many who'd had a known family history of aneurysms. The result also was replicated in studies of mice and zebrafish. Researchers could actually see blood pooling in the heads of the fish, which have clear skin, soon after manipulating the gene.
"It's truly a fascinating discovery," Kim said, "because, prior to this research, hardly anyone knew what this gene did or how it worked."
The coming years will be exciting, Kim said. Researchers will be racing to understand how the obscure gene works and what it can teach them about the origins of aneurysms.
He's even contemplated testing himself for the genetic mutation. He hasn't yet, he said, "but I might have to."
Most of his peers probably don't realize Kim's obsession with aneurysms has been fueled, at least in part, by personal tragedy.
His uncle died abruptly of a brain hemorrhage at the age of 34, when Kim was still a child. The same fate awaited three of his four grandparents.
Kim, one of the world's foremost neurosurgeons, acknowledged those events have quietly shaped his work, though he tries not to make too big a deal of the personal connection.
"I would say so," he said. "Absolutely."
While he's relishing this latest milestone, he knows there's much more work to be done before a treatment can be developed and lives saved. That could take another 15 or 20 years, he suspects.
"God willing," Kim said, "I'm hoping I'm around to see it."