Self-healing nematodes offer new hope for nerve repair

As the interface between our external environment and our internal perception, our nerves underpin every one of our basic bodily functions. But they are surprisingly delicate: they communicate using long, thin, cable-like structures called axons, which are woefully susceptible to breaking.

Once broken, they are notoriously difficult to repair.

But in new research published in Science Advances, researchers from the University of Queensland (UQ) have found that a tiny nematode, Caenorhabditis elegans – the invertebrate equivalent of the lab rat – may hold the secret to a pioneering new approach to treating nerve damage.

As scientists’ favourite worm, C. elegans has long been prized as a model organism. Its simple, transparent body allows easy tracking of individual cells throughout their development, and many key insights into human disease have arisen from studies of these unassuming roundworms.

In spite of their simple body plan and decades of scrutiny, C. elegans continue to deliver astonishing new discoveries.

In 2015, Dr Massimo Hilliard and his team at UQ’s Queensland Brain Institute discovered that the nematode had the remarkable ability to self-heal. They found that C. elegans could spontaneously re-join two separated axon fragments, in a process called axonal fusion.

Digging deeper into the molecular mechanisms that underpin this healing, Hilliard and his team have now identified an enzyme known as ADM-4 as an essential regulating protein that serves as the molecular glue, or fusogen, during nerve repair.

“We have shown that animals lacking ADM-4 cannot repair their nerves by fusion,” Hilliard says.

“ADM-4 must function within the injured neuron to stabilise the fusogen EFF-1 and allow the membranes of the separated nerves to merge.”

Good news for worms, but what about more complex creatures?

Hilliard says there’s promise on that front: the similarity between ADM-4 and a known mammalian gene opens up the possibility of one day harnessing this process in humans.

Study first author, Dr Xue Yan Ho, is likewise excited about the possibility of inducing worm-like self-healing capabilities in humans.

“Our goal is to uncover the molecules and understand their role in nerve repair in C. elegans,” Ho says.

“If we can understand how to control this process, we can apply this knowledge to other animal models. The hope is that one day, we can induce the same mechanical process in people who have had a nerve injury.

“We are still a long way from this goal, but the discovery of ADM-4’s role is an important step forward.”

Associate Professor Victor Anggono, who helped to define the molecular mechanisms of nerve regeneration, believes this could deliver significantly better outcomes for patients than traditional approaches.

“Using neurosurgery to stitch together damaged nerves has limited success,” Anggono says.

“A different approach using gene technology to directly provide the molecular glue, or activate the fusogen regulator ADM-4, or using pharmacology to activate these components, may facilitate complete regeneration.”