E 'news these days that an international team of researchers has discovered a new treatment against stroke. The treatment is based on the inactivation of the enzyme NOX4 responsible for most of the damage to nerve cells in the moments after the ictal phenomenon, because of its ability to form Peroxide hydrogen (H2O2). The drug capable of inhibiting the NOX4 already exists and is called VAS2870 .
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An international team of researchers has found a new way to treat stroke by blocking the activity of an enzyme responsible for most of the damage caused to brain cells during the period following a stroke. The findings represent an important step forward in the search for new treatments for ischemic stroke, which is the second leading cause of death worldwide.
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Previous work on treatments for stroke have concentrated on oxidative stress, which is caused by " reactive oxygen species (ROS), however, the care of patients with antioxidants has failed in clinical trials. In this latest study, scientists from Australia, Germany, Netherlands and United Kingdom have adopted a different approach, the first thing preventing the production of ROS.
They found that most of the damage caused in the period following a stroke can be attributed to an enzyme called NOX4 , which produces hydrogen peroxide (H2O2), a chemical compound commonly used in products to bleach.
The team has designed GM mice that lack the gene that produces NOX4, when these mice were affected by stroke, suffered minor damage to their brains than mice with working versions of the gene NOX4.
In particular, mice lacking the gene NOX4 higher scores in tests to assess their neurological and motor functions and coordination.
The effects of the deletion of the gene NOX4 were the same in mice and in male and female young and old animals, an important issue if we consider that the stroke is mainly a disease of the elderly and that the sex of the patients affect its outcome.
Having established the role of NOX4 in damage from stroke, the team decided to test ways to exploit this knowledge for therapeutic purposes. Fortunately, there is already a drug called VAS2870 designed to block the activity of NOX4.
The team found that treatment of mice with VAS2870 has the same effect as deletion of the gene NOX4, thus reducing brain damage and improving neurological function, even when administered hours after the stroke. In addition, inhibiting the action of NOX4 in this way does not seem to have caused problems to other parts of the body where the NOX4 is normally active, such as blood vessels supplying the kidneys and heart.
"The NOX4 is therefore the most promising new therapeutic target to reduce oxidative stress in general, and brain damage caused by the stroke in particular," the researchers conclude.
Ischemic stroke occurs when blood flow is blocked to the brain, or due to a drop in blood pressure or due to occlusion of blood vessels. If the blood supply to the brain is not restored quickly, the affected brain tissue may die, causing serious mental and physical disabilities and, at worst, death. The elderly are most at risk of stroke, and with an aging population, the incidence of this serious medical condition is likely to grow.
Today, there is only one drug approved for the treatment of stroke. However, it is not perfect. "It involves the dissolution of clots in the brain to eliminate the insufficient blood circulation, but increases the risk of bleeding in the brain," says Christoph Kleinschnitz, the main author of the study, University of Würzburg in Germany. Indeed, the effectiveness of the drug is described as "moderate," and can be used only about 10% of patients. The remaining 90% is excluded because of contraindications.
Attempts to develop more drugs to treat stroke have so far failed, although many have proven effective in animals, they were not worked in men. "The consequence was that many pharmaceutical companies have withdrawn from research into new medicines in this sector," the researchers note.
The pharmacologist Professor Harald Schmidt, University of Maastricht in the Netherlands led the research. He believes that the strategy of blocking oxidative stress at the source could be applied to other important health problems. He says, "Inhibiting now source of hydrogen peroxide or oxygen radicals might be the solution for so long sought to cure even heart attacks, heart failure, cancer and other forms of degeneration of nerve cells such as Parkinson's and Alzheimer's disease. "
The effects of the deletion of the gene NOX4 were the same in mice and in male and female young and old animals, an important issue if we consider that the stroke is mainly a disease of the elderly and that the sex of the patients affect its outcome.
Having established the role of NOX4 in damage from stroke, the team decided to test ways to exploit this knowledge for therapeutic purposes. Fortunately, there is already a drug called VAS2870 designed to block the activity of NOX4.
The team found that treatment of mice with VAS2870 has the same effect as deletion of the gene NOX4, thus reducing brain damage and improving neurological function, even when administered hours after the stroke. In addition, inhibiting the action of NOX4 in this way does not seem to have caused problems to other parts of the body where the NOX4 is normally active, such as blood vessels supplying the kidneys and heart.
"The NOX4 is therefore the most promising new therapeutic target to reduce oxidative stress in general, and brain damage caused by the stroke in particular," the researchers conclude.
Ischemic stroke occurs when blood flow is blocked to the brain, or due to a drop in blood pressure or due to occlusion of blood vessels. If the blood supply to the brain is not restored quickly, the affected brain tissue may die, causing serious mental and physical disabilities and, at worst, death. The elderly are most at risk of stroke, and with an aging population, the incidence of this serious medical condition is likely to grow.
Today, there is only one drug approved for the treatment of stroke. However, it is not perfect. "It involves the dissolution of clots in the brain to eliminate the insufficient blood circulation, but increases the risk of bleeding in the brain," says Christoph Kleinschnitz, the main author of the study, University of Würzburg in Germany. Indeed, the effectiveness of the drug is described as "moderate," and can be used only about 10% of patients. The remaining 90% is excluded because of contraindications.
Attempts to develop more drugs to treat stroke have so far failed, although many have proven effective in animals, they were not worked in men. "The consequence was that many pharmaceutical companies have withdrawn from research into new medicines in this sector," the researchers note.
The pharmacologist Professor Harald Schmidt, University of Maastricht in the Netherlands led the research. He believes that the strategy of blocking oxidative stress at the source could be applied to other important health problems. He says, "Inhibiting now source of hydrogen peroxide or oxygen radicals might be the solution for so long sought to cure even heart attacks, heart failure, cancer and other forms of degeneration of nerve cells such as Parkinson's and Alzheimer's disease. "
Source: Cordis (10/04/2010)
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