18 June 2018

The spinal cord will be restored by gene therapy

Gene Switch can Cure Spinal cord Injuries

Asvat Valieva, Neuron studies based on the materials of IoPPN: Gene therapy restores hand function after spinal cord injury in rats.

Researchers with the help of gene therapy have successfully restored limb movements in rats suffering from paralysis due to spinal cord injury. This is the subject of an article in the journal Brain (Burnside et al., Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury).

People with spinal cord injuries often lose the ability to perform everyday activities that require coordinated hand movements: for example, writing, brushing teeth or holding a glass of water. Restoring hand function is a priority task for patients and can significantly increase the patient's independence and quality of life. Currently, there are no treatment methods that trigger the regeneration of spinal cord tissues, although there are already some successes with stem cells, which we recently reported.

The authors of this work tested a new gene therapy, whose tasks included starting the regeneration of damaged tissues in the spinal cord, regulated by a general spectrum antibiotic.

"We can control exactly how long the treatment will take using the "switching" gene. This means that we can accurately calculate the optimal amount of time needed for recovery. Gene therapy makes it possible to regenerate large areas of the spinal cord with just one injection, and having a "switch", we can now stop the process when it is no longer necessary," says Professor Elizabeth Bradbury from the Institute of Psychiatry, Psychology and Neuroscience (IoPPN).

After traumatic spinal cord injury, the dense scar tissue formed prevents the formation of new connections between neurons. Gene therapy provokes cells to produce an enzyme called chondroitinase. This enzyme partially destroys scar tissue and allows neural networks to regenerate.

Since spinal cord injuries in humans most often occur at the cervical level and affect the work of all four limbs, the researchers performed gene therapy on rats with similar injuries. This is because rats and humans use a similar sequence of coordinated movements to reach and capture an object.

The "inclusion" of the therapeutic gene after the destruction of spinal cord tissues at the cervical level after two months allowed the animals to gently reach for sugar and grab it. After histological examination of the affected area, the scientists were convinced that new connections had formed there between the nerve cells.

regeneration.jpg

Active neural connections in the restored spinal cord on the left in the micrograph are displayed using fluorescence in turquoise color, and on the right with functional PET imaging are shown in warm shades.

To overcome the problem with the immune system, which labeled the switch gene as foreign, researchers together with colleagues from the Netherlands created a design in which they added an "invisible gene" that hides the switch from immunity.

However, gene therapy is not yet ready for human trials. The researchers found that a small amount of the gene remains active even after being turned off. Now they are working on a complete shutdown of the gene and are moving towards work with other animal species.

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