The enzyme that brings about damage and death of nerve cells in stroke patients has been identified by a Dutch-German medical research team.
The enzyme NOX4 produces hydrogen peroxide, a caustic molecule also used in bleaching agents. Inhibition of NOX4 by an experimental new drug in mice with stroke dramatically reduces brain damage and preserves brain functions, even when given hours after the stroke.
Stroke researcher, Christoph Kleinschnitz, from University of Wurzburg, Germany, explains "Ischemic stroke is the second leading cause of death worldwide. Today, only one approved therapy exists. The effectiveness of this therapy is rather moderate, and, importantly, it can only be used in about 10pc of patients; the other 90pc are excluded due to contraindications."
"Thus, there is a huge medical need for better stroke therapies. One such candidate mechanism is oxidative stress. However, approaches to apply antioxidants have failed in clinical stroke trials. This study proposes an entirely new strategy by inhibiting the relevant source of hydrogen peroxide and preventing its formation," Kleinschnitz added.
Importantly, elimination of the NOX4 gene in mice did not result in any abnormalities and therefore no obvious side-effects are to be expected from a future NOX4 inhibitor drug.
This could be demonstrated with the detailed systemic phenotyping analysis by the team of the German Mouse Clinic at the Helmholtz Zentrum M|nchen, Germany.
The identification of NOX4 as an enzyme with a key role in killing nerve cells after a stroke in mice makes NOX4 inhibition currently the most promising new therapeutic approach in this often deadly or disabling disease in humans.
Harald Schmidt from Maastricht University, Netherlands, suspects that 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."
These findings will be published next week in the online, open access journal PLoS Biology.