Gene therapy could promote healing in brain, spinal cord injuries

UT Southwestern scientists will study whether preemptively dialing up LZK in mice affects the severity of an injury. (Gerry Shaw)

The human body responds to a spinal cord injury by making scar tissue, effectively sealing the wound but preventing the creation of new tissue. Scientists at UT Southwestern have discovered a "genetic trigger" that could be targeted to improve how the brain and spinal cord recover from injury. 

The team focused on the LZK gene in the astrocytes, which are star-shaped supportive cells. The function of astrocytes in the healthy central nervous system are well known, but their role in response to injury is less understood. 

Working in mice with spinal cord injuries, the team found that deleting the LZK gene reduced astrogliosis—the increase in astrocyte numbers in response to injury and infection—and resulted in a bigger wound. Overexpressing LZK boosted astrogliosis and led to the creation of a smaller scar. The hope is that this means a more effective recovery from injury. 

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"[Akin] to wound repair following skin lesions, reactive astrocytes and the glial scar also have beneficial roles in confining the injury site, repairing the blood-brain barrier, and limiting the spread of inflammation," the researchers said in their paper, which appeared in Cell Reports. 

While the study focused on spinal cord injury, Goldberg thinks the findings could have implications in other brain injuries, including stroke and concussion. 

"We've known that astrocytes can help the brain and spinal cord recover from injury, but we didn't fully understand the trigger that activates these cells," said Mark Goldberg, M.D., chairman of neurology and neurotherapeutics at UT Southwestern, in a statement. "Now we'll be able to look at whether turning on the switch we identified can help in the healing process." 

RELATED: Large-scale study to bring precision medicine to traumatic brain injury treatment 

Scientists have found potential treatments for CNS injury in the unlikeliest of places. University of Guelph researchers found that geckos have a type of stem cell called radial glia in their tails, which allows them to detach their tails to escape predators and regrow the severed appendage later. In response to injury, the radial glia quickly proliferate and produce proteins that generate a new spinal cord. They think their discovery could be used to create new treatments for people with spinal cord injuries. 

As for traumatic brain injuries, Australian researchers combined short peptides with a compound made from a sugar found in seaweed to make a scaffold that resembled healthy brain tissue. In the lab, they injected the scaffold into a damaged brain and found that it prevented scarring and promoted healing

Goldberg's lab at UT Southwestern is now planning to look into the effects of astrogliolisis in stroke and spinal cord injuries. Specifically, they will determine whether preemptively dialing up LZK in mice affects the severity of an injury, and then measure how the formation of a smaller scar aids or impedes recovery.