Gene therapy found to restore hand function in rats, in research from King’s College London

Researchers based at King’s College London have shown in recent work that gene therapy can restore hand function after spinal cord injury in rats.

Patients suffering with a spinal cord injury can often lose the ability to perform everyday tasks requiring coordinated hand movements. If this form of hand function can be regained quality of life and patient independence could be significantly improved. Currently, there are no regenerative treatments available for spinal cord injuries.

After suffering a spinal injury, dense scar tissue usually forms. It is this tissue that prevents new connections being made between nerve cells.

With the gene therapy, the researchers found that an enzyme was produced by cells (chondroitinase) that broke down the scar tissue and allowed networks of nerve cells to regenerate.

“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 from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN). “This means we can hone in on the optimal amount of time needed for recovery. Gene therapy provides a way of treating large areas of the spinal cord with only one injection, and with the switch we can now turn the gene off when it is no longer needed.”

In their study, the researchers gave the gene therapy to rats with spinal injuries that most closely resembled the kind of injuries that occur in humans after traumatic impacts such as car crashes or falls.

“Rats and humans use a similar sequence of coordinated movements when reaching and grasping for objects,” explained Dr Emily Burnside from the IoPPN. “We found that when the gene therapy was switched on for two months the rats were able to accurately reach and grasp sugar pellets. 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.”

However, the team needed to overcome a problem with the immune system recognising and removing the gene switch mechanism. To overcome this they collaborated with colleagues in the Netherlands to include a ‘stealth gene’, which hides the gene switch from the immune system.

“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,” added Professor Joost Verhaagen at the Netherlands Institute for Neuroscience. “This is the first time a gene therapy with a stealth on/off switch has been shown to work in animals.”

Although not ready yet for human trials, the team have been working on ways to ensure the gene ca be shut down completely and then will look to move on to trials in larger species.

The research is funded by the Medical Research Council, the International Spinal Research Trust and Wings for Life, and published in the journal Brain.