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Gene therapy dissolves scar tissue to heal rat spinal cord, reversing paralysis

18 June 2018
Appeared in BioNews 954

A novel approach to gene therapy has restored limb control to rats paralysed after spinal cord injury, new research has found. 

The rats were given two months of a gene therapy that made cells produce an enzyme that broke down the scar tissue that had formed after injury. This allowed nerve cells to form new connections around the site of the damage. 

'We found that when the gene therapy was switched on for two months the rats were able to accurately reach and grasp sugar pellets,' said Dr Emily Burnside from King's College London's Institute of Psychiatry, Psychology and Neuroscience. 'We also found a dramatic increase in activity in the spinal cord of the rats, suggesting that new connections had been made in the networks of nerve cells.'

The study, published in the journal Brain, involved 85 rats, which had similar spinal injuries to those found in humans, randomly assigned to three groups. Rats in the group receiving gene therapy treatment were compared to those given non-functional gene therapy or no treatment. 

The gene therapy was given by injection and controlled by a molecular 'stealth switch', so that its level of activity was controlled by an additional drug. 

'What is exciting about our approach is that we can precisely control how long the therapy is delivered by using a gene switch,' said Professor Elizabeth Bradbury, study researcher at King's College London. 'This means we can hone in on the optimal amount of time needed for recovery.'

The enzyme induced by the gene therapy to break down the scar tissue, chondroitinase, was produced at very low levels when the gene switch was on. In future, the researchers hope that it will be possible to completely turn off the gene when treatment is no longer needed, minimising the negative side effects of longer-term therapy.

'The use of a stealth gene switch provides an important safeguard and is an encouraging step toward an effective gene therapy for spinal cord injury,' said Professor Joost Verhaagen, study author at the Netherlands Institute for Neuroscience, Amsterdam. 'This is the first time a gene therapy with a stealth on/off switch has been shown to work in animals.'

Speaking to the BBC, Dr Mark Bacon from the charity Spinal Research said: 'The data is some of the most compelling I've seen demonstrating restoration of skilled forelimb function… Transferred to the clinic, this research could be life-changing for the millions of people worldwide with paralysis caused by a spinal cord injury.'

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