By Ken Sakamoto, Star-Bulletin
Dr. Bo K. Siesjo says stroke "is a tragedy to all
affected by it, not only the patients, but family."

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Isle team
develops drugs to
fight stroke

Drugs that halt damage
and further chances for recovery
could reach test stage
in 2 years

By Helen Altonn
Star-Bulletin

Drugs to reduce or eliminate the devastating effects of a stroke may be possible soon because of a research team in Hawaii.

There is no good treatment now for the nation's No. 3 killer, says Dr. Bo K. Siesjo, world-renowned researcher heading the group at the Queen's Medical Center.

The best thing is a drug known as t-PA (tissue plasminogen activator) which permits "reflow" of blood after a brain attack, he said, but it also has risks.

T-PA must be given within three hours after the start of symptoms to get blood to flow again through the obstructed vessel and halt damage.

Siesjo's group is working with Centaur Pharmaceuticals Inc. to develop anti-stroke drugs that have no side effects and can fight brain damage three to five hours after a clot starts.

He said there have been some "wonderful breakthroughs" and he expects some promising new drugs to be ready for clinical testing within two or three years.

A mandatory retirement age of 65 at Sweden's University of Lund led the distinguished scientist to Hawaii three years ago. He accepted an offer as research director in the Center for the Study of Neurological Disease, part of Queen's new Neuroscience Institute.

With him came his group of seven researchers and about $600,000 in grants.

Siesjo is one of few scientists outside the United States to receive National Institutes of Health funding, noted Dr. Marek A. Mirski, medical director of the Neuroscience Institute.

He said Siesjo has led research on tissue injury in the brain for the last quarter of the century. "He's probably at the very top of the game now in the world. . . . He's practically a Nobel laureate, and he may win it yet. He's a giant."

Siesjo said his mother died of a stroke at age 87, many years after he became a stroke researcher.

Halting damage to the brain

Trained as a neurosurgeon, Siesjo said he gradually became interested in disease and sick cells, realizing that to do something about stroke, or brain attack, "you had to know basic science ... biochemical sequences. It has been a long struggle."

His internationally recognized group has been doing cellular and molecular work to learn what goes wrong in the brain, how this leads to blood loss and cell death, and what they can do to interfere with it, he said.

When a clot is formed in the blood vessel of a stroke patient, it can be dissolved in perhaps two to three hours, Siesjo said. "The question now is, 'Is this going to leave a real scar, damage? Is it possible to do anything for a patient after ischemia?' "

Ischemia is any condition leading to decreased blood flow to the tissue, he said.

When that happens, the brain is deprived of oxygen, and nerve cells die within minutes.

The researchers are experimenting with drugs called "spin traps" that scavenge free radicals and offer a good chance of reducing or possibly preventing damage, Siesjo said.

Extending victim's chances

Free radicals are unstable, poisonous molecules that spread like wildfire with great potential for brain damage.

They breed more radicals, aggressively attack other molecules in cells and tissues, and break down the cellular structure.

Siesjo said about 10 to 15 drugs are in clinical trials for strokes but he predicts "the effect will be marginal."

His lab is working on a new generation of nontoxic drugs that "do not disturb functions you need to have for evaluating the type of stroke it is," he said.

One drug under study could be given by paramedics in an ambulance without waiting for a diagnosis, he said. "There is plenty of time using a drug like that, a second window of opportunity." In a hospital, it could be given after three hours, he said.

Working with a 'superteam'

The researchers have found that calcium levels may become too high in cells after a stroke or heart attack, Siesjo said, so new drugs are based on blocking calcium influx into cells before they die.

They also are looking at ways to improve performance of surviving cells so "they can take over some functions of dead neighbors," he said.

Scientists around the world are working on stroke problems and a lot of progress is being made toward finding ways to prevent deaths and disabilities, Siesjo said. "It is a tragedy to all affected by it, not only patients but family."

Siesjo said he's still developing his laboratory and building up his scientific group. They're also collaborating with other centers to study mechanisms of neurological disease, he said.

"The field has become so extremely tricky and creative, it is best to create a kind of superteam," he said. "We're extremely lucky to collaborate with some of the best minds."

‘Brain attack’ signals
urgency of stroke care

By Helen Altonn
Star-Bulletin

Whenever a person is en route to the Queen's Hospital by ambulance or arrives at the emergency room with stroke symptoms, a "stroke code" is launched.

The hospitalwide system to alert appropriate medical staff of a stroke patient is part of a comprehensive new clinical and research neuroscience program at Queen's.

Some stroke treatments must be given very soon after symptoms appear, so "it's important to treat stroke nowadays like one treats heart attack," said Dr. Marek Mirski, medical director of the Neuroscience Institute.

"Minutes count," he said. "Hence, the name 'brain attack,' adopted by the American Academy of Neurology, as the name for this." The academy wants the public to realize a stroke is serious but can be treated with quick medical care, he said.

A stroke code triggers a team approach for rapid evaluation and treatment of patients in the emergency department, neuroscience intensive care unit, or elsewhere in the hospital, Mirski said.

"You need a well-organized structure in the medical center to safely offer these types of medications because of the risk and time window.

"Very few medical centers around the country have their act together to evaluate all the patients they could," Mirski added.

At Queen's, he said, "we're sort of following a step behind treatment of heart attacks in the emergency room."

It's tougher to diagnose subtle signs of neurological disease than heart trouble, he said. "There is no easy EKG (electrocardiogram) one does in ER to rule out a neurological problem."

Arthur A. Ushijima, Queen's president and chief executive officer, said the hospital is "focused on developing and enhancing the health of our community."

"We're trying to build the base of intellectual capital in neuroscience and working with the University of Hawaii and collaborators of these researchers around the world," he said.

Expertise, technology and full monitoring capabilities were assembled in the Neuroscience Institute two years ago to provide the best possible care in the Pacific to patients with neuroscience illnesses, Mirski said.

It includes:

A neuroscience intensive care unit "for accepting and triaging (assigning medical priorities) and caring for patients with head injuries, stroke and neurological diseases."

A stroke program where new drugs and treatment options are being investigated and developed, such as clot-busting drugs and drugs called "neuro-protectants." Several are in clinical trials in the hospital, Mirski said.

The only "neurointerventional" program in the Pacific with specialists offering nonsurgical techniques to treat vascular problems. Specially trained radiologists at the University of California in San Francisco collaborate with Queen's, coming here on a regular basis to see patients.

Sophisticated equipment to analyze and treat vascular problems, including a state-of-the-art imaging center to diagnose strokes in a couple minutes, instead of 30 minutes to an hour.

A training program for emergency medical teams and a stroke-education program for the community, physicians and nurses, not only here but in Asia.

Learn about stroke causes, treatment in talks this week Free public lectures on brain attack will be presented by the Queen's Medical Center and by Straub Clinic & Hospital in observance of National Stroke Awareness Month. The American Heart Association is co-sponsoring the Queen's program about strokes, prevention and treatments at 6:30 p.m. Wednesday at Tenney Theatre, to be conducted by Drs. Marek Mirski and Cherylee Chang. Free blood pressure screenings will be available from 5:30 to 6:30 p.m., before the lecture. For information and reservations, call 537-7117. At Straub's event, from 9 to 11 a.m. Saturday, Drs. Leo Maher and Roger White will discuss causes of stroke and the newest treatments; it will be at Thomas Square Center, 846 South Hotel St., Room 210. Free blood pressure and hypertension screenings will be offered after the session. For information on Straub's program, call 522-4395.