UK researchers track genetic trail of ALS, one version of which is more common around Cumberland Gap than anywhere else

Debby Taylor and Dr. Edward Kasarskis talk at the headquarters
of Cumberland Gap National Historical Park. (Alex Stilz photo)

Two University of Kentucky researchers are on the genetic trail of amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease. Their detective story has not reached its end, but it is told in fascinating fashion by Eric Boodman of Stat, the medicine-and-science publication of The Boston Globe.

The story is based around the Cumberland Gap, where Kentucky meets Tennessee and Virginia. "This corner of Appalachia runs thicker with a particular form of inherited ALS than almost anywhere else," Boodman reports, and its chief tracker is Dr. Edward Kasarskis, the neurologist who discovered the cluster, beginning with one family in 1993. A family member on her deathbed told him of a relative who knew "the whole family history," Kasarskis told Boodman, but she "just refused to talk to me."

"He tried to piece it together himself, making calls, jotting names and dates on bits of paper," Boodman writes. "Families were tight-lipped, though, and he didn’t have much luck. He turned to other things." But a decade later, he mentioned his quest to UK research coordinator Debby Taylor, who had been "mapping her own family history on Ancestry.com, and she offered to try with software what hadn’t worked by hand. Within a day, she had 12 pages of names." How, it has "grown into a 250-page digital family tree, with around 6,700 names, eight generations, two intertwined families, and a lot of ALS."

Now, "Taylor and Dr. K know that among the 5,000 annual diagnoses of ALS in the U.S., only around 10 percent are inherited. They know there are over 30 different major genes in which a mistake might be causing the disease. They know that the mutation they’re studying is among the rarer ones, affecting a gene called FUS. What they still don’t know is why certain family members with the mutation get the disease, and others don’t." Kasarskis cited a man who lived into his 90s, had then gene, and never developed the disease -- but three of his children did, and two others got the gene from him.

Though they have a roadmap, the research is slow. They "can’t just look up an address and show up at someone’s door. “Until they develop an illness and come to medical attention, they’re just a name on a chart, on a pedigree,” Kasarskis said. “We can’t legally go doing cold calls: ‘Hey, George, how’s it going? By the way, have you developed your ALS yet?’” So they must "wait for patients to come to them," Boodman reports. "They don’t ask about participating in research right away; there is no cure for ALS, and the diagnosis can be devastating. . . . Some people don’t trust Taylor and Dr. K. Others don’t see how this research could possibly help them. Yet others simply refuse to accept the diagnosis."

Taylor told Boodman, “If you tell your fiancé that there’s ALS in your family, do you think he or she is really going to marry you? So this is not anything that people want to talk about.” But enough of them talked to Boodman to make a great story. Read it here.