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New treatment hope for brain and spinal cord injuries

Friday May 15th, 2020

A repurposed treatment could dramatically reduce swelling after brain and spinal cord injury, according to the findings of a major global study.

The breakthrough in treating central nervous system (CNS) oedema could be significant because existing options are limited to putting patients in an induced coma or performing risky surgery.

The new treatment, developed by an international team of scientists working at Aston University, University of Birmingham and University of Wolverhampton, UK, with Harvard medical School, USA, University of Calgary, Canada, Lund University, Sweden, and Copenhagen University, Denmark, uses trifluoperazine (TFP) to alter the behaviour of aquaporins.

Writing in Cell, they describe testing the treatment on injured rats, finding that those given a single dose of the drug at the trauma site recovered full movement and sensitivity in as little as two weeks, compared to a control group that did not receive treatment and had motor and sensory impairment beyond six weeks after the injury.

The treatment counteracts the cells' normal reaction to a loss of oxygen in the CNS caused by trauma. Under such conditions, cells quickly become 'saltier' because of a build-up of ions, causing a rush of water through the aquaporins, which makes the cells swell and exerts pressure on the skull and spine. This build-up of pressure damages fragile brain and spinal cord tissues, disrupting the flow of electrical signals from the brain to the body and vice versa.

However, this latest study found that TFP, used to treat people with schizophrenia and other mental health conditions, can stop this from happening.

Focusing on astrocytes, the researchers found TFP prevents the protein calmodulin from binding with the aquaporins. By halting this action, it reduces the permeability of the cells.

Professor Roslyn Bill of the Biosciences Research Group at Aston University said: "This discovery, based on a new understanding of how our cells work at the molecular level, gives injury victims and their doctors hope. By using a drug already licensed for human use, we have shown how it is possible to stop the swelling and pressure build-up in the CNS that is responsible for long-term harm.”

Dr Zubair Ahmed of the University of Birmingham's Institute of Inflammation and Ageing added: "This is a significant advance from current therapies, which only treat the symptoms of brain and spinal injuries but do nothing to prevent the neurological deficits that usually occur as a result of swelling. The re-purposed drug offers a real solution to these patients and can be fast-tracked to the clinic."

Dr Mootaz Salman, Research Fellow in Cell Biology at Harvard Medical School, said: "This novel treatment offers new hope for patients with CNS injuries and has huge therapeutic potential. Our findings suggest it could be ready for clinical application at a low cost in the very near future.”

Kitchen P, Salman M, Halsey A et al. Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema Cell 14 May 2020

https://doi.org/10.1016/j.cell.2020.03.037

Tags: A&E | Brain & Neurology | Europe | North America | UK News

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