Research Suggests a Diabetes Medication
May Be Good As Stroke Treatment, Too
HOUSTON–(April 10, 2007)–A diabetes medication named rosiglitazone may be good for reducing secondary stroke injury, too, according to a study to be published online April 24 in the Annals of Neurology by researchers in the Stroke Program of the Department of Neurology at The University of Texas Medical School at Houston.
About 700,000 Americans each year suffer a stroke, and there are different types. The ischemic type is caused by a blocked blood vessel and the intracerebral hemorrhagic (ICH) type is caused by a ruptured blood vessel. This Annals of Neurology study focused on ICH.
Xiurong Zhao, M.D., lead author of the Annals of Neurology study, and Jaroslaw Aronowski, Ph.D. (right).
Rosiglitazone reduced secondary ICH injury by almost 70 percent during animal trials in the laboratory of Jaroslaw Aronowski, Ph.D., associate professor of neurology for stroke research. Xiurong Zhao, M.D., research assistant professor, was lead author on the study titled “Hematoma Resolution as a Target for Intracerebral Hemorrhage Treatment: Role of Peroxisome Proliferator-Activated Receptor γ in Microglia/Macrophage.”
ICH accounts for 15 percent of strokes, and high blood pressure is the primary cause. Toxic for surrounding cells, leaking blood takes space in the brain, kills tissue and can affect the ability to speak and think. “The situation can go from bad to worse quickly,” fellow investigator Nicole R. Gonzales, M.D., said.
Mortality after ICH approaches 50 percent at one year, according to Aronowski, and only 20 percent of patients regain functional independence at six months.
There are currently no approved treatments, according to Gonzales, for both the primary injury caused by ICH and the aftereffects of hematoma, also referred to as secondary injury. “This is a disease where we are way behind the curve in terms of treatment compared with other types of stroke,” said Gonzales, assistant professor of neurology.
Emergency room therapies focus on aggressive management of the patient’s blood pressure, as well as general patient support, she said. Brain surgery is sometimes recommended for the appropriate patients.
Rosiglitazone reduced neurological deficits in mice with ICH by 27 percent after seven days, 49 percent after 14 days and 67 percent after 21 days. The deficit reduction was also noticed in mice treated with rosiglitazone prior to experiencing ICH, according to Aronowski, which suggests that medication could be beneficial in diabetic patients already taking the medication who develop ICH. Similar results were experienced during in vitro trials.
Rosiglitazone was effective in mice when administered up to 24 hours after ICH. “We are currently trying to figure out the optimal timing and optimal dosage which will produce the best results,” he said.
The next step involves the establishment of safety in patients with stroke and these trials may proceed quickly because diabetics are already taking rosiglitazone. “It is easier to get approval for something that is proven as opposed to a new drug,” Aronowski said.
Rosiglitazone is marketed as a prescription medication for adult onset or Type II diabetes by GlaxoSmithKline under the trade name Avandia. The medication can improve insulin sensitivity.
While it’s unclear exactly how rosiglitazone works, scientists believe the medication impacts a transcription factor peroxisome proliferator activated receptor gamma (PPARγ). “PPARγ protects the brain and amplifies the action of macrophages, the tiny cells that engulf foreign particles in the brain and remove them,” said Aronowski. “We’re enhancing the body’s ability to take blood out of the brain.”
Gonzales believes rosiglitazone could be an important part of ICH treatment but not the only part. “Treating ICH will most likely require multiple therapies. If we are able to demonstrate the same findings clinically, rosiglitazone could be the first beneficial medication for patients with ICH,” she said.
The study was supported by the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke, and the American Heart Association.
Other contributors to the study from the UT-Houston Stroke Program include: Guanghua Sun, M.D., research assistant; Jie Zhang, research assistant; Roger Strong, research scientist; and James C. Grotta, M.D., the Roy M. and Phyllis Gough Huffington Distinguished Chair in Neurology, also professor and chairman of neurology and director of the Stroke Program.
Weitao Song, M.D., at Baylor College of Medicine, also contributed to the study.