Valerie Verge
Valerie Verge

Nerve knowledge

A research team led by Valerie Verge at the University of Saskatchewan has discovered an important molecular worker in the repair shop of the body’s nervous system, a finding that brings them a step closer to new treatments for debilitating nerve injuries.

The molecule is called Luman, a nerve cell protein discovered by Vikram Misra in the Western College of Veterinary Medicine while he was investigating the common cold sore virus. Verge and Misra, together with PhD student Zhengxin Ying, wondered if Luman had a more general role in informing sensory neurons about events such as nerve injury.

Luman acts like order sheets in a repair shop, explained Verge, a professor in the U of S College of Medicine and director of the Cameco MS Neuroscience Research Center at City Hospital in Saskatoon. When a nerve is injured, the order comes in to send out proteins to make repairs. Luman goes to the cell nucleus, gets the cell's DNA to generate templates for the proteins needed for repair, and then transfers those specs to the cell's protein factory to build what is needed.

She explained that in sensory neurons, Luman's role is complicated by distance. Like other cells, neurons have a main body and axons—long, branching filaments that carry nerve impulses from the brain to the extremities and back. Verge said a series of experiments by Ying show Luman is not only an order taker, but also a messenger, shuttling back to the neuron information critical for re-growing the damaged axon.

"This is a brand-new concept, that all the way out in the axon there are molecules that can sense the stress of a nerve injury and send that signal back to the cell body to further regulate axon repair," she said. "This is another major piece of the puzzle (in understanding how nerves heal)."

The research is published in the Proceedings of the National Academy of Sciences.

Verge and her colleagues will now be looking to find out more about which Luman-regulated proteins are the active players in repairing injured nerves.

"We're now also in the lab looking at strategies and ways that might rev this (repair process) up," Verge said. "Can we then develop new therapeutics that target those, or find ways to boost this Luman response to make this repair even more effective?"

Another project in the Verge lab approached nerve repair from a different angle: repairing the insulating sheath surrounding axons using direct electrical stimulation.

Like electrical wires, nerves have a form of insulation called myelin that protects them and allows more efficient signal conduction, she said. In diseases such as multiple sclerosis, myelin is destroyed, causing everything from physical disability to trouble thinking or chronic pain.

Verge said research has already shown that direct electrical stimulation helps nerves re-grow after an injury, but could it help reinsulate nerves whose myelin has been damaged by disease?

In work conducted by her PhD student Nikki McLean and colleagues from Alberta and Ontario recently published in the journal PLOS ONE, Verge said it was discovered that direct electrical stimulation of the nerve not only helped it rebuild its myelin, but the stimulation also revved up the associated immune system response.

"The results in the paper are really stunning in that a single one-hour bout of electrical nerve stimulation helped both the repair of the myelin, as well as helped the axon protect itself against destruction," Verge said.

She cautions that the results are promising but there is still much work to be done. The experiments used a rat model and surgical intervention, which is impractical in humans, especially if the damaged nerves are in the brain or spinal cord.

"The one thing I don't want to do is create false hope, but I can say there are a number of different strategies that we're testing," she said. "If we can electrically activate the neurons and their damaged axons, make them more active, will they remyelinate (re-insulate) better? And the answer appears to be yes."

Verge explained one strategy might be to stimulate more nerve activity naturally through exercise. Physical rehabilitation programs designed to deliver just the right amount of stimulation could be part of the solution.

"This holds tremendous promise, because we already know from past studies that (electrical stimulation) helps injured neurons to regenerate," she said. "Now we know it can also help axons … to remyelinate. So the big challenge is on: can we do this with less-invasive approaches or approaches that will stimulate larger areas?"
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