Leukemia drug could save lives of stroke patients

Studies in mice reveal why tPA may cause brain damage
The drug tPA is the most effective treatment currently available for stroke patients, but its safety is limited to use within the first three hours following the onset of symptoms. After that, tPA may cause dangerous bleeding in the brain. However, in a study published today in Nature Medicine, investigators from the Stockholm Branch of the Ludwig Institute for Cancer Research (LICR) and the University of Michigan Medical School show that these problems might be overcome if tPA is combined with the leukemia drug, imatinib (Gleevec®). The results demonstrate that imatinib greatly reduces the risk of tPA-associated bleeding in mice, even when tPA was given as late as five hours after the stroke had begun. The LICR team, in collaboration with the Karolinska University Hospital in Stockholm, is now planning a clinical trial with imatinib in stroke patients.

According to the World Health Organization (WHO), 80 percent of the 15 million strokes that occur each year are caused by the type of blood clots in the brain that tPA can dissolve. Today, less than 3% of patients with this type of stroke receive tPA because the narrow safety window has often passed by the time a stroke patient reaches a hospital and is diagnosed. If the planned clinical trial with stroke patients in Sweden confirms the findings of the present study, there is great promise that imatinib or similar drugs could be administered to stoke patients to increase the therapeutic window of tPA.

The basis for this novel proposal is the key growth factor PDGF-CC, which has now been discovered to control the blood brain barrier (a structure that normally shields the brain from the blood). When tPA acts on PDGF-CC, the blood-brain barrier becomes porous and can start to leak. Imatinib inhibits the detrimental effect of PDGF-CC by binding to its receptor PDGFR alpha, seemingly without hindering tPA's therapeutic effect, which is to break down clots that have lodged in the brain's blood vessels.

"Ten years ago our research group identified the growth factor PDGF-CC, and we are now very excited having unraveled a mechanism in the brain involving this factor", says Professor Ulf Eriksson, who leads the LICR team. "This finding has indeed the potential to revolutionize the treatment of stroke."

Source: Ludwig Institute for Cancer Research

Related stories:

Mouse studies suggest daily dose of ginkgo may prevent brain cell damage after a stroke
Working with genetically engineered mice, researchers at Johns Hopkins have shown that daily doses of a standardized extract from the leaves of the ginkgo tree can prevent or reduce brain damage after an induced stroke.
Unusual case of a woman who suffered stroke during sex
Minutes after having sexual intercourse with her boyfriend, a 35-year-old woman suddenly felt her left arm go weak. Her speech became slurred and she lost feeling on the left side of her face.
High blood pressure after stroke should not necessarily rule out use of clot-busting treatment
Patients who require therapy to lower their blood pressure following a stroke do not appear to be at a higher risk for bleeding or other adverse outcomes after receiving anti-clotting therapy, according to a report in the September issue of Archives of Neurology, one of the JAMA/Archives journals.
New hope for stroke patients
If a stroke patient doesn't get treatment within approximately the first three hours of symptoms, there's not much doctors can do to limit damage to the brain.
Stroke study reveals key target for improving treatment and suggests that Gleevec may help
Research in mice shows why tPA carries risks as well as benefits, and suggests that Gleevec or other drugs could prevent problems
For over a decade, the drug called tPA has proven its worth as the most effective emergency treatment for the most common kind of stroke. But its promise is blemished by two facts: tPA can cause dangerous bleeding in the brain, and its brain-saving power fades fast after the third hour of a stroke.
Old antibiotic may find new life as a stroke treatment
An old intravenous antibiotic may have new life as a stroke treatment, researchers say. Minocycline appears to reduce stroke damage in multiple ways – inhibiting white blood cells and enzymes that, at least acutely, can destroy brain tissue and blood vessels, respectively, says Dr. David Hess, chair of the Department of Neurology in the Medical College of Georgia School of Medicine. The broad-spectrum antibiotic also seems to reduce cell suicide in the minutes and hours following a stroke, enabling more cells to recover.
Researchers fine-tune clot-busting treatment for bleeding in brain
A multicenter study led by Johns Hopkins doctors has fine-tuned the dosage and timing for administering clot-busting tissue plasminogen activator (tPA) to patients with strokes caused by bleeding within the brain. The treatment, as reported this week at the European Stroke Conference in Nice, France, has been shown to dramatically decrease death and disability in patients with this typically lethal subset of stroke.
Post-stroke clot-busting therapy beneficial for patients on aspirin
Patients given a clot-busting drug following stroke appear to have better outcomes if they were already taking anti-platelet medications, despite an apparent increased risk for bleeding in the brain, according to an article posted online today that will appear in the May 2008 print issue of Archives of Neurology.

News discussion:

Medicine & Health news