Zebrafish Could Help Repair Human Spinal Cord Injuries

By Pat Anson, Editor

A freshwater fish popular in many home aquariums might hold the key to repairing damaged spinal cords in humans.

In a study published in the journal Science, Researchers at Duke University say the zebrafish is able to completely heal its spine -- even after it was severed -- because of a protein that helps to rebuild damaged spinal nerves.

"This is one of nature's most remarkable feats of regeneration," said the study's senior investigator Kenneth Poss, a professor of cell biology and director of the Regeneration Next initiative at Duke. "Given the limited number of successful therapies available today for repairing lost tissues, we need to look to animals like zebrafish for new clues about how to stimulate regeneration."

Poss and his colleagues say when the zebrafish's spinal cord is severed, dozens of genes are activated by the injury. Within days, they produce new molecules and proteins to bridge the gap between the severed spine. One of the proteins, called connective tissue growth factor (CTGF), appears to play a key role in regenerating glia nerve cells.

Within 8 weeks, new nerve tissue has filled the gap in the spinal cord and the zebrafish has fully reversed its paralysis.

"The fish go from paralyzed to swimming in the tank. The effect of the protein is striking," said lead author Mayssa Mokalled, a postdoctoral fellow at Duke. “We thought that these glial cells and this gene must be important.”

The zebrafish belongs to the minnow family and is native India, Pakistan and the Himalayan region. It is widely used in scientific research because if it’s regenerative abilities, and was the first vertebra to be cloned. A 2012 study published in The Journal of Neuroscience also documented the fish’s ability to bridge the gap between spinal nerve cells.

Humans and zebrafish share many genes, and the human CTGF protein is nearly 90% similar in its amino acids to the zebrafish’s.

Remarkably, when Duke researchers added the human version of CTGF to the severed spinal cords in zebrafish, it boosted regeneration and the fish began swimming two weeks after the injury.

Healing damaged spinal cords is more complex in mammals, in part because scar tissue forms around the injury. Researchers say CTGF is probably not sufficient on its own for people to regenerate their spinal cords, but further animal studies are needed.

"Mouse experiments could be key," Mokalled says. "When do they express CTGF, and in what cell types?"

The Duke research team also plans to follow up with other proteins that were secreted after injury, which may provide further hints into the zebrafish's ability to regenerate nerve cells.

"I don't think CTGF is the complete answer, but it's a great thing to have in hand to inform new ways to think about the real challenge of trying to improve regeneration," Poss said.

This research was supported by the National Institutes of Health, the Max Planck Society, and Duke University School of Medicine. Duke is seeking patent applications related to the research.