A collaborative study between scientists at the University of Malta (J. Vella, C. Zammit, and M. Valentino) and the University Peninsula Schools of Medicine and Dentistry (S. Doyle, D.B. Hansen, P. Bond, G. Harper, and R. Fern) has led to the discovery of a new drug, QNZ-46, that was shown to protect the rodent brain after a stroke. Previous attempts to find a drug that prevents brain damage after stroke have proved unsuccessful and this new research offers the possibility of a new exciting treatment.
Published in 'Nature Communications', the study identified the source of the glutamate, an amino acid neurotransmitter that is the cause of the damage produced in stroke and led to the discovery that the drug QNZ-46 protects the brain against this damage.
Professor Mario Valentino said that the results from this collaborative research could become a precursor to pharmaceutical trials. Most ischemic strokes involve both white and gray matter, yet 20% of strokes predominantly involve white matter. In addition, cerebral white matter is sensitive to ischemic injury at all stages of development and in particular to the protective nerve sheath (myelin) of its nerve fibres that leads to severe functional deficits in affected individuals. We have shown that the drug QNZ-46 prevents damage to the myelin of the nerve fibres and protects them from the toxic effect of the glutamate that is released by the damaged nerve cells.
A recognized authority on white matter injury, Professor Robert Fern said that this is the first study to show direct evidence of vesicular fusion within different cellular components in white matter, a process that was thought to be absent from white matter.
Preliminary results have shown that the new treatment with the drug QNZ-46 would benefit patients at high risk of suffering a stroke or other brain condition in which excessive and uncontrolled release of glutamate is the main agent that leads to death of brain cells. The study demonstrated that the trapped glutamate acts on specific receptors located on the myelin and leads to its disintegration and loss of brain function. Results from this study convincingly show that QNZ-46 prevents this damage.
The full study, entitled Vesicular glutamate release from central axons contributes to myelin damage (doi: 10.1038/s41467-018-03427-1) was funded by the University of Plymouth and the Biotechnology and Biological Sciences Research Council and the Alfred Mizzi Foundation through the RIDT, and is available for viewing in 'Nature Communications'.