Ten years ago, the first drug to reduce the damaging effects of stroke, TPA, hit the market. Today, it remains the only such drug.
Eileen Hellems doesn’t remember having a stroke. Her friend told her what happened. She suffered the brain attack while hosting a dinner party.
Eileen says, "I guess my eyes got glassy, my lip turned, and um, I guess my left arm dropped. And she came over and said I think she’s having a stroke."
Eileen had a blood clot in the brain, the most common type of stroke. She was rushed to the hospital and treated quickly with the intravenous clot-dissolving drug TPA.
“I have been very blessed," she says. "All I have is a weakened left side.”
Eileen is one of the lucky few to get TPA. Doctors are reluctant to use it because it increases the risk of bleeding in the brain and must be given within three hours of the first symptoms.
Dr. Curtis Benesch says, "It passes very, very quickly. A lot has to happen within those first three hours."
Scientists at the University of Rochester are studying a drug that may prevent stroke damage in a different way. It’s called Activated Protein C, or APC, and is a form of a natural protein that dissolves blood clots. Laboratory studies found it does a lot more.
Dr. Berislav Zlokovic says it, "was originally thought to be just anticoagulant then is proven to have some strong anti-inflammatory functions, and then we were adding to it, it has cell protective functions."
Its ability to keep brain cells from dying may be the key to reducing stroke's devastating effects.
Dr. Benesch says, "The goal would be to provide patients with a drug like APC that could potentially salvage some of those cells that have been injured."
It might also expand the treatment window beyond three hours.
Dr. Zlokovic says, "We do ultimately hope that APC could be given, um, more than after four hours, probably nine hours, within nine hours; eventually within twelve hours."
But APC has a long way to go. It has to be tested in people and many promising stroke drugs have failed in human trials.
Dr. Benesch says, "We really are desperate to find other means of treating patients who come in with an acute stroke."
Until then, preventing stroke and getting immediate treatment are critical.
A stroke is a medical emergency but people often don’t get treatment in time. Warning signs include: sudden numbness or weakness, severe headache, confusion, or the inability to see, speak or walk.
Fast Facts:About 700,000 strokes occur each year in the U.S. The condition kills about 157,000 annually and is a leading cause of long-term disability.
Ischemic strokes may be treated with a medication, called TPA, which works to break up the clot.
Treatment with TPA needs to be given within three hours of the onset of symptoms but only about 15 percent of stroke patients get to the hospital within that three-hour window.
Researchers at the University of Rochester are testing a drug, called Activated Protein C , for ischemic stroke. The medication may expand the treatment window time – up to 12 hours.
A stroke occurs when blood flow to the brain is disrupted. It can be caused by a blockage (ischemic stroke) or bleeding (hemorrhagic stroke). Ischemic strokes are the most common type, accounting for about 83 percent of strokes. There are two main types. In a cerebral thrombosis, a blood clot forms in an artery feeding the brain and blocks the flow of blood. A cerebral embolism occurs when a blood clot from another area of the body travels through the circulatory system and becomes wedged in a narrower artery of the brain.
Hemorrhagic strokes occur when a weakened blood vessel in the brain ruptures, or bursts. They are less common than ischemic strokes (accounting for about 17 percent of cases), but are often much more deadly. A hemorrhagic stroke is usually caused by one of two main types of problems. An aneurysm is a weakening in the wall of an artery. Like a tire with a weak spot, the affected area can stretch under the pressure of blood and eventually burst. An arteriovenous malformation is a cluster of abnormal blood vessels. These vessels are weaker than normal blood vessels and are prone to rupture.
According to the American Stroke Association, about 700,000 strokes occur every year in the U.S. About 157,000 Americans die from stroke. It’s a leading cause of long-term disability in this country.
Treating Ischemic Stroke
A stroke is a medical emergency. The sooner a patient gets to the hospital, the faster treatment can be given and the greater the likelihood of reducing brain damage. When doctors determine a stroke is caused by a blockage, a patient may be given the clot-busting drug, tissue plasminogen activator (tPA). The medication is given intravenously to slowly dissolve and break up the clot.
Currently, tPA is the only clot-busting drug approved by the FDA for ischemic stroke. But there are some limits to its use. Therapy must be initiated within three hours of the onset of symptoms. But many patients don’t get the hospital in time to start the treatment. Stroke victims may not be aware of the signs of stroke or may not recognize the symptoms as a stroke. One study found only 15 percent of stroke patients get to the emergency room within that three-hour window and under 7 percent were eligible for TPA.
There are other risks associated with tPA. Treatment doesn’t always work – especially when clots are very large. Research shows the drug can be toxic to brain cells, and also increases the risk of brain hemorrhage by about six percent.
Researchers at the University of Rochester are testing a different treatment for ischemic stroke, called activated protein C (APC). The medication is a form of the natural protein in the body that inhibits blood coagulation. Currently, APC is approved for treatment of complications of sepsis. However, preliminary studies suggest it may be useful in treatment of stroke-inducing clots.
In animals with lab-induced ischemic stroke, treatment with APC successfully treated blockages and improved survival rates. Further investigation found the treatment also reduced inflammation in the brain and provided some protection for brain cells. More importantly, the drug could be given much later after the onset of symptoms - perhaps expanding the treatment window to a total of 12 hours.
APC is now in a phase I study for humans with ischemic stroke. Investigators are unsure if APC will be used alone or in conjunction with tPA. If used in combination, APC may provide protection for brain cells and ameliorate the potential toxic effects of tPA. It may also allow patients more time to get to the hospital for treatment.
In the meantime, doctors say prompt treatment is vital. Everyone should be aware of the warning signs of stroke and seek medical help if the symptoms appear. Those signs include: Sudden numbness or weakness in an area of the body
Sudden confusion or problems understanding or speaking
Sudden difficulty walking, loss of balance or dizziness
Sudden severe headache of an unknown cause
Web ResourcesAmerican Stroke Association Web site
For information on stroke:
National Institute of Neurological Disorders and Stroke Web site.
National Stroke Association Web site.