14 DAY TRIAL // A Dutch-German medical research team made an incredible breakthrough by finding the enzyme responsible for the death of nerve cells after a stroke.
The team led by Harald Schmidt from Maastricht University, Netherlands, and Christoph Kleinschnitz, University of Würzburg, Germany, has found that the NOX4 enzyme produces hydrogen peroxide, a caustic molecule also used in bleaching agents.
The researchers experimented a new drug in mice with stroke, and found that it managed to reduce brain damage significantly while preserving brain functions, even if it was administrated several hours after the stroke.
“Ischemic stroke is the second leading cause of death worldwide, and today, only one approved therapy exists,” said stroke researcher, Christoph Kleinschnitz, who is also Germany's Young Scientist of the Year 2008.
“The effectiveness of this therapy is rather moderate, and, importantly, it can only be used in about 10% of patients; the other 90% are excluded due to contraindications, thus, there is a huge medical need for better stroke therapies,” he explained.
“One such candidate mechanism is oxidative stress, however, approaches to apply antioxidants have failed in clinical stroke trials.
This is why “this study proposes an entirely new strategy by inhibiting the relevant source of hydrogen peroxide and preventing its formation.”
The mice whose NOX4 gene was removed, did not develop any abnormalities so there should not be any problems or side-effects with a future NOX4 inhibitor drug, and the detailed systemic phenotyping analysis by the team of the German Mouse Clinic at the Helmholtz Zentrum München, Germany, could prove it.
Discovering that the NOX4 enzyme is responsible for killing nerve cells after a stroke is a huge step and it actually makes NOX4 inhibition the most promising therapeutic approach there is.
Stroke is an often deadly or disabling disease in humans and this discovery could be vital for many people, and might also treat other diseases, like pharmacologist, Prof. Schmidt suspects.
The findings “may have implications for other disease states in which hydrogen peroxide or related oxygen radicals are suspected to play a major role but where antioxidant or vitamin therapies have failed.
“Inhibiting now the source of hydrogen peroxide or oxygen radicals may represent the long-sought solution to treating also heart attacks, heart failure, cancer, and other forms of nerve cell degeneration such as in Parkinson's or Alzheimer's disease,” he added.
This discovery will be published next week in the online, open access journal PLoS Biology.