Gene therapy with 'off switch' restores hand movement in rats with spinal cord injury

Illustration of three DNA helices
Rats who underwent gene therapy for two months were able to relearn skilled hand movements. (Darwin Laganzon)

When the spinal cord is injured, it forms scar tissue that stops the creation of new tissue. Delivering gene therapy to the injury site is a promising way to repair that damage, but it comes with safety concerns, namely uncontrolled gene expression down the line. Researchers from King's College London have addressed this challenge with a gene therapy that can be switched off once it has treated an injury. 

Their treatment prompts production of the enzyme chondroitinase, which breaks down scar tissue and allows neurons to regenerate. It is delivered using a dual vector system, which enables an on-off switch that can be triggered with the antibiotic doxycyline. To avoid interference from the immune system, the team hid the gene switch using a "stealth gene," according to a statement. 

They successfully tested the approach in rats with spinal injuries that were similar to the types of spinal injuries that humans sustain after traumatic events such as car crashes or falls.

The researchers saw results when the gene therapy was switched on for as few as two and a half weeks: "transient treatment ... is sufficient to promote improvement in sensory axon conduction and ladder walking performance," they wrote in the study, which appears in the journal Brain. Rats that underwent longer-term treatments were able to re-learn skilled hand movements, they added. 

"Rats and humans use a similar sequence of coordinated movements when reaching and grasping for objects. 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 Elizabeth Bradbury, a professor of regenerative medicine and neuroplasticity at King's College's Institute of Psychiatry, Psychology & Neuroscience, in the statement. "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."

In a similar tack, UT Southwestern scientists found a "genetic trigger" that can be targeted to reduce scarring in spinal cord injury. Overexpressing the LZK gene in astrocytes—the star-shaped supportive cells of the nervous system—boosted a process that increases astrocyte numbers in response to injury and infection.

The treatment developed at Kings College London needs some fine-tuning before it will be ready for use in humans. At the moment, a small amount of the chondroitinase gene stayed active, even when the therapy had been switched off. The team is now working to block the gene completely and move into studies in larger animals. 

"This preclinical study could have a significant impact for tetraplegic individuals, for whom recovery of hand function is an important determinant of independence, and supports the ongoing development of chondroitinase gene therapy towards clinical application for the treatment of spinal cord injury," the researchers wrote in the study. 

Training Course

BioBasics: Biotech For The Non-Scientist

BioBasics: Biotech for the Non-Scientist is a two-day course for those who want to better understand the science driving the industry. The course starts with basic scientific concepts and quickly delves into the causes of genetic and infectious disease and the therapeutic strategies used to mitigate disease. The latest innovations in immunotherapies, gene therapy, checkpoint inhibitors, CAR-T and more are explained.

Suggested Articles

The week’s biotech discoveries included eight mutations that contribute to cardiomyopathy and an enzyme that promotes basal-like breast cancer.

IRhythm’s ECG patch was able to improve atrial fibrillation diagnoses and lower numbers of ER visits by shifting patients to outpatient settings.

Cold Genesys is developing its lead asset as a single agent and in combination therapies and has taken it through phase 2 in bladder cancer.