Gene Therapy Research Restores Hand Function after SCI

Some of the latest news in spinal cord injury (SCI) research, which comes from the United Kingdom, shows promising results for gene therapy. The chondroitinase gene therapy involves helping rats re-learn hand functions after sustaining spinal cord injuries. Researchers, predominantly based at King’s College London, published a research paper in June on their work with rats that sought to increase skilled hand functions in rats with cervical spinal cord injuries.

Background on Cervical Spinal Cord Injuries

The spinal cord isn’t one singular cord; it is a group of 31 nerve bundles. Because most spinal cord injuries are caused by blunt force trauma (automobile accidents, falls, acts of violence, and sports), the spinal cord builds up scar tissue at the injury site that impedes communication between the brain and the rest of the body.

Cervical spinal cord injuries, which affect the uppermost region of the spinal cord, are the most deadly forms of SCI and affect the spinal cord levels known as C1-C7. Many spinal cord injury survivors experience the loss of sensory and motor functions in all extremities, including one or both of their hands, post-injury. This means that they can’t use their hands to pick up a cup, groom themselves, or perform other independent functions.

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How the Gene Therapy Works

In the gene therapy study, the researchers wanted to study and compare the short and long-term gene therapy results in rats with cervical spinal cord injuries. Using clinically-available broad-spectrum antibiotic known as doxycycline, they were able to control the expression of an enzyme known as chondroitinase ABC (ChABC), which is used to help break down some of the adverse components of the dense spinal cord scar tissue with the goal of helping new nerve fibers to grow.

The ChABC enzyme was used to remove some of those negative scar tissue factors, known as chondroitin sulfate proteoglycans (CSPGs), which inhibit neuronal expression. The CSPGs are secreted by reactive glia — cells that surround and insulate neurons — after a spinal cord injury causes damage to the central nervous system. Using a novel immune-evasive dual vector system to control the gene under a “doxycycline-inducible regulatory switch,” they could add or remove those beneficial ChABC enzymes to see how they affected the rats’ hand functions. Essentially, the researchers could control when the gene was delivered and for how long.

Using an immune-stealth modification, the researchers were able to control the delivery of the enzyme to the rats’ injured tissue in the area of their spinal cord injuries. Prior to their injuries, the rats were trained to perform specific tasks — ladder walking and grabbing sugar cubes from a narrow passage inside of a clear plastic box. The study showed that rats who received 2.5 weeks of treatment showed improvement in their sensory axon conduction and ladder walking performance. However, rats that received long-term treatment (eight weeks) showed “significantly improved function, with rats able to accurately grasp and retrieve sugar pellets.”

The Potential Application for Human SCI Survivors

This gene therapy research provides hope in the spinal cord injury research frontier and shows promise for the future. However, although no adverse effects have yet been documented following ChABC delivery to an injured or uninjured spinal cord, researchers cautiously note the concern of possible adverse effects that could result from long-term ChABC gene therapy that could eventually lead to maladaptive remodeling or negatively affect neuroplasticity.

According to the study:

“Our novel immune-evasive gene switch represents a powerful experimental tool to temporally explore the effects of ChABC therapeutic treatment and an encouraging step towards generating a more clinically-feasible ChABC gene therapy strategy. Its use reveals temporally dependent, task-specific, functional effects where short term administration is sufficient to enable recovery of sensorimotor integration during walking and long term administration confers additional benefit to skilled reaching and grasping after cervical contusion injury. This preclinical study represents a significant advance since recovery of hand function is the highest rated priority for improving functional outcome in individuals with tetraplegia.”

At Spinal Cord, we’re excited about the advancement of this research and excitedly await what future research in this area may hold. We’ll continue to keep you apprised of new and exciting spinal cord injury research on our blog.

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Topics: Research

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