Scientists find clue to cell damage after stroke
Scientists have found that an enzyme is responsible for the death of nerve cells after a stroke and say an experimental drug that dramatically reduced brain damage in mice may also offer hope for humans.
Previous attempts to design drugs that can protect the brain from damage after a stroke have had limited success.
Dutch and German researchers said on Tuesday that their work showed a potential new approach to treating stroke, which is the most common cardiovascular problem after heart disease and kills an estimated 5.7 million people worldwide each year.
In tests on mice, the scientists found that an experimental drug, known as VAS2870 and being developed by the German biotech firm Vasopharm, dramatically reduced brain damage and preserved brain functions, even when given hours after the stroke.
The indications are very strong that the same mechanism may apply for human stroke, said Harald Schmidt from Maastricht University in the Netherlands, who led the study with Christoph Kleinschnitz from Wurzburg University in Germany.
Ischaemic stroke is the most common kind of stroke, caused by a clot or other blockage disrupting the flow of blood to the brain.
The only currently available treatment is a clot-busting drug called a t-PA, or tissue plasminogen activator, but it must be given within three hours of a stroke and only around five to 10 percent of stroke victims get it.
Scientists facing a paucity of effective stroke drugs have been investigating whether tissue damage after stroke may be linked to a mechanism called oxidative stress, in which reactive oxygen species (ROS) accumulate within a cell.
Previous experimental drugs designed to soak up loose ROS after stroke have failed in late-stage clinical trials. A compound from AstraZeneca called NXY-059 proved to be an expensive flop for the Anglo-Swedish drugmaker in 2006.
But in this study, published in the Public Library of Science (PLoS) Biology journal, Schmidt and Kleinschnitz focused on finding and then trying to block the source of ROS.
The enzyme they identified is called NOX4, and by blocking NOX4 with the experimental drug in mice with stroke, they dramatically reduced brain damage.
They also found that eliminating the gene linked to NOX4 in mice did not result in any abnormalities, suggesting that no obvious side-effects are to be expected from a future NOX4 inhibitor drug, they wrote in the study.
This approach focuses on keeping the neurons alive -- it preserves the neurons and brain function, Schmidt said in a telephone interview. We show here that if you identify the real source (of oxidative stress), there is a huge potential benefit if you are then able to inhibit it.
Schmidt said the findings may also have implications for other diseases which are assumed to be linked to oxidative stress, such as heart attacks and some cancers, and for other forms of nerve cell degeneration such as in Parkinson's or Alzheimer's disease.
We now have a concept that we can follow in all these conditions -- identify the source, try to inhibit it, and see if that makes a difference, he said.