Protein completely restores motor function; scientists hope it will help humans.
People with impaired mobility after a stroke soon may have a therapy that restores limb function long after the injury, if a supplemental protein works as well in humans as it does in paralyzed rats. Two new studies by UC Irvine biologists have found that a protein naturally occurring in humans restores motor function in rats after a stroke. Administered directly to the brain, the protein restores 99 percent of lost movement; if it’s given through the nose, 70 percent of lost movement is regained. Untreated rats improve by only 30 percent.

James Fallon mobilizes existing stem cells, causing them to proliferate, migrate and eventually differentiate into new cells (shown by the red area back left) that fill in the damaged brain, returning function to to the stroke victim. photo: Daniel A. Anderson

“No drugs exist that will help a stroke after a few days. If you have a stroke, you don’t have many treatment options,” said James Fallon, psychiatry & human behavior professor and senior coauthor of the studies. “Now we have evidence there may be therapies that can repair damage to a significant degree long after the stroke. It’s a completely unexpected and remarkable finding, and it’s worth trying in humans.”

The studies, carried out by UCI postdoctoral researcher Magda Guerra-Crespo, chronicle the success of a small protein called transforming growth factor alpha, which plays critical tissue forming and developmental roles in humans from just after conception through birth and into old age.

“TGF alpha has been studied for two decades in other organ systems but never before has been shown to reverse the symptoms of a stroke,” Guerra-Crespo said. No lasting side effects were observed.

In the first study, published in the journal Neuroscience, scientists sought to learn whether TGF alpha administered directly to the brain could help rats with stroke-induced loss of limb function, typically on one side - as is seen in humans.

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HOUSTON - Giving clot-busting drugs to patients who wake up with stroke symptoms appears to be as safe as giving it to those in the recommended three-hour window, according to researchers at The University of Texas Medical School at Houston. The results of the study, “Thrombolytic Therapy for Patients Who Wake Up With Stroke,” are published in the March issue of Stroke, a journal of the American Heart Association.

“The results of our study serve as the only published material of patients who woke up with ischemic stroke symptoms and were treated with thrombolytic therapy,” said Andrew Barreto, M.D., lead author and assistant professor of neurology at the UT Medical School at Houston. “It stands as the only support for the safety of stroke treatment in wake-up stroke patients.”

Stroke occurs when blood flow to the brain is interrupted by a blockage or a rupture in an artery, depriving brain tissue of oxygen. It is the third-leading cause of death behind heart disease and cancer. According to the American Stroke Association, nearly 800,000 Americans suffer a stroke each year - one every 40 seconds. On average, someone dies of stroke every three to four minutes.

According to protocol from the U.S. Food and Drug Administration, thrombolytic medications such as intravenous tissue plasminogen activator (tPA) should be given to patients with a blockage within three hours of the onset of stroke symptoms.

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In a large clinical trial involving patients with coronary artery disease, use of B vitamins was not effective for preventing death or cardiovascular events, according to a study published in the August 20 issue of JAMA.”Observational studies have demonstrated that the concentration of total homocysteine in blood is associated with risk of coronary artery disease and stroke,” the authors provide as background information. Plasma total homocysteine levels can be lowered by oral administration of folic acid and vitamin B12. In this study, the authors’ objective was “to evaluate the effects of homocysteine-lowering treatment with folic acid plus vitamin B12 on mortality and cardiovascular events.”

Marta Ebbing, M.D. of Haukeland University Hospital, Bergen, Norway and colleagues, conducted a randomized controlled study with 3,096 patients in two Norwegian hospitals between 1999 – 2006. Patients were randomly assigned to one of four groups receiving a daily oral dose of one of the following treatments: folic acid, 0.8mg, plus vitamin B12 , 0.4mg, plus vitamin B6 , 40mg (n= 772); folic acid plus vitamin B12 (n = 772); vitamin B6 alone (n = 772); or placebo (n = 780). Patients were scheduled for follow-up visits with an interview, clinical examination, and blood sampling at one month, one year, and at a final study visit. The main outcome measure (primary end point) was a composite of all-cause death, nonfatal acute myocardial infarction (heart attack), acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.

The study was stopped early because of concerns among the participants about preliminary results from another similar Norwegian study suggesting no benefits from the treatment and an increased risk of cancer from the B vitamins.

“Mean (average) plasma total homocysteine concentration was reduced by 30 percent after 1 year of treatment in the groups receiving folic acid and vitamin B12,” the authors report. “During a median (midpoint) 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7 percent): 219 participants (14.2 percent) receiving folic acid/vitamin B12 vs. 203 (13.1 percent) not receiving such treatment and 200 participants (13.0 percent) receiving vitamin B6 vs. 222 (14.3 percent) not receiving vitamin B6.”

“We could not detect any preventive effect of intervention with folic acid plus vitamin B12 or with vitamin B6 on mortality or major cardiovascular events among patients with stable coronary artery disease undergoing intensive conventional treatment. We found a numerically lower incidence of stroke and higher incidence of cancer in the groups receiving folic acid, but these observations were not statistically significant,” the authors conclude. “Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.”