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Searching for a Stroke Gene

MacReady, Norra

Department: Clinical Trial Watch

Norra MacReady is a book author whose health and medical articles have appeared in The Economist and Condé Nast Traveler.

For more information on this trial, contact the Mayo Clinic in Jacksonville at 904-296-3815.

For clinical trials listed in the AAN's journal Neurology, visit



Roger Scharf wasn't supposed to have a stroke. Scharf was doing everything right: He watched his weight, didn't smoke, maintained his cholesterol between 150 and 180 mg/dL, and generally lived a healthy life.

But just over a year ago, when he was only 58 years old, he had a stroke so severe that he required a feeding tube for four months. Today he's able to eat normally again, to live independently and to generally care for himself, but he had to retire from his job as a civil engineer and still has some residual weakness on his left side. “I can get around OK as long as I don't have to walk too long or too far,” says Scharf, a resident of St. Augustine Beach, Fla.

In retrospect, it's not surprising that he suffered a stroke. His doctors discovered that despite his exemplary habits, he had extensive fatty deposits, or plaque, in the blood vessels that travel from the heart through the neck and into the lower part of the brain. In some areas, the plaque was so thick that it blocked the artery by 70 percent. His stroke occurred when a blood clot formed in his body, entered an obstructed blood vessel and lodged there, cutting off the blood flow to that part of his brain.

But why someone who took such good care of himself would suffer such a massive stroke at such a young age was a mystery. What's more, Scharf's older sister had had a stroke about two years earlier. Both of these facts point to a genetic propensity for stroke that could have tipped the scales against his lifestyle.

And so Scharf was invited to participate in the Siblings With Ischemic Stroke Study (SWISS), led by principal investigator James Meschia, M.D., of the Mayo Clinic in Jacksonville, Fla.

“Until recently, most of the research on stroke has focused on environmental risk factors like diet and smoking,” says Dr. Meschia, an associate professor of neurology at the Mayo Clinic College of Medicine. “Yet we know that some people have genetic mutations that interact with environmental factors to increase their risk of other neurological disorders, like Alzheimer's disease, Parkinson's disease and multiple sclerosis.”

Studies of twins and family histories conducted in the 1970s and 1980s suggested that some people might be genetically more prone to stroke than others, but how much of a person's stroke tendency is inherited remains unclear.

Siblings who share a medical condition most likely have certain genetic features that can help doctors zero in on the gene or genes that influence the risk of developing that condition, Dr. Meschia explains. Once those genes have been identified, they can then be examined in the general population to see if other people have similar genes that place them at risk.

The study is open to anyone over the age of 18 who has had a stroke, has a sibling who also has had a stroke, and is identified as a candidate by specialists at the Mayo Clinic or at any of 50 participating centers around the country, Dr. Meschia says. Participants must have had an ischemic stroke, in which a blood clot blocks the circulation in an artery leading to the brain, as it did with Roger Scharf. This most common type occurs in more than 80 percent of people who have had a stroke. The other main type is a hemorrhagic stroke, which occurs when a cerebral blood vessel bursts and starts leaking blood into the brain. People who have had that type of stroke are not eligible for the SWISS trial.

The study is actually fairly easy for the volunteers. All they have to do is allow the investigators access to their medical records, answer questions about their own and their families' medical histories, and provide a blood sample, which can be collected at home by a home health agency. They must also provide a packet of study information to all of their siblings and invite them to participate. The scientists then analyze all the data to see if there is anything in the participant's genetic information that indicates a higher-than-average risk of stroke.

“The most exciting part of the study is that we will be in a position to gain unique insight into whether a particular gene is related to an increased risk of stroke,” Dr. Meschia says. “If a gene is indeed related to risk, it may one day be a target for developing new drugs.”

People with high-risk genes could also be advised to take particularly aggressive methods to lower their chances of having a stroke, he adds. Those steps generally include a very strict diet and exercise regimen as well as cholesterol-lowering drugs.

So far the SWISS investigators have enrolled 200 sibling pairs, toward a goal of 300 pairs. (Siblings who are interested can contact the Mayo Clinic in Jacksonville and go through the same evaluation as the brother or sister who is already enrolled.)

Preliminary findings point to similarities among siblings in the types of stroke they have and the age at which the strokes occur.

For his part, Roger Scharf is hoping his sister will enroll in the study. He's as curious as anyone, he says, to learn whether a stroke gene runs in his family.

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Facts on Strokes

  • More than 700,000 strokes occur each year in the U.S.
  • Every 3 minutes, someone dies of a stroke — the third-leading cause of death in the U.S. (right behind heart disease and cancer).
  • 15% to 30% of stroke survivors are permanently disabled.
  • Some 4 million Americans currently live with the effects of a stroke.
  • 75% of strokes occur in people over age 65.
  • The risk of stroke doubles with each decade of life after age 55.
  • In 2006, stroke will cost American society about $58 billion.

Sources: National Institute of Neurological Disordersand Stroke; American Stroke Association.

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