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Scientists have identified a protein that may be key to recovery of spinal cord injuries in humans and lead to therapies for repairing lost tissues. A freshwater zebrafish can repair its own spinal cord completely after being severed – a paralyzing and often fatal injury for humans. Scientists at Duke University in the US found a particular protein important for the process which could generate new leads into tissue repair in humans.
“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,” said Kenneth Poss, professor at Duke University. When the zebrafish’s severed spinal cord undergoes regeneration, the first cells extend projections into a distance tens of times their own length and connect across a wide gulf of the injury – forming a bridge.
By eight weeks, new nerve tissue has filled the gap and the animals have fully reversed their severe paralysis. To understand what molecules were potentially responsible for this remarkable process, scientists studied all genes whose activity abruptly changed after spinal cord injury.
Of dozens of genes strongly activated by injury, seven coded for proteins that are secreted from cells. One of these, called connective tissue growth factor (CTGF), was intriguing because its levels rose in the supporting cells, or glia, that formed the bridge in the first two weeks following injury.
“We were surprised that it was expressed in only a fraction of glial cells after the injury. We thought that these glial cells and this gene must be important,” said Mayssa Mokalled, a postdoctoral fellow in Poss’ group. Indeed, when they tried deleting CTGF genetically, those fish failed to regenerate. Humans and zebrafish share most protein-coding genes, and CTGF is no exception. The human CTGF protein is nearly 90 per cent similar in its amino acid building blocks to the zebrafish form.
When the team added the human version of CTGF to the injury site in fish, it boosted regeneration and the fish swam better by two weeks after the injury. “The fish go from paralysed to swimming in the tank. The effect of the protein is striking,” Mokalled said.
The second half of the CTGF protein seems to be the key to the healing, the group found. It is a large protein, made of four smaller parts, and it has more than one function. That might make it easier to deliver and more specific as a therapy for spinal injuries. The study was published in the journal Science.