The spinal cord works like a fiber-optic cable, carrying millions of messages in the blink of an eye between brain and body.
When that cable gets cut or crushed, as it does in about 10,000 people a year who break their backs, it frequently leads to lifelong paralysis because the long, spindly nerves in the spine can't heal themselves.
Now, researchers at the Mayo Clinic are in a scientific race to do what until recently was believed to be impossible -- reverse paralysis. Researchers at the clinic have coaxed severed spinal nerves in rats to grow by building a bridge across the gap in the cord and seeding it with special molecules.
It will be five to 10 years before their work and similar nerve regeneration research elsewhere lead to treatment in people, but progress -- and hope --is accelerating, researchers say.
"There is a lot of excitement building in spinal cord repair and regeneration," said Dr. Michael Fehlings, a professor of neurosurgery at the University of Toronto and director of the Krembil Neuroscience Center there.
Progress cannot come too soon for Dr. Michael Yaszemski, a spinal surgeon at the Mayo Clinic and one of the lead researchers in the nerve regeneration project. Every week he sees patients, most of them men, whose lives, like that of actor Christopher Reeve's, were transformed by a car accident, sports injury or violent act.
"Sometimes they get a little better," he said. "But it takes a while for them to realize that we are helping them live as a paralyzed person."
There are 200,000 to 300,000 nerves in the spinal cord that branch to the arms, torso and legs. Extending from each nerve cell is an axon, a thread-like fiber that can be up to 2 feet long, or longer in someone the size of Michael Jordan. These are the pathways for the nerves that the brain uses to tell the heart to beat and muscles to move, and they also tell the brain what is cold, hot or soft.
Hard-wired
The nerves are contained inside the long chain of vertebrae. When those bones are crushed or dislocated, they damage or sever the delicate nerve fibers. For reasons that are not well understood, other surrounding nerves begin to die, too, leaving behind scar tissue and fluid-filled cavities within the spinal cord. Nerves elsewhere in the body can regenerate, but not those in the spinal cord -- the system is just too complex to rewire itself, said Dr. Anthony Windebank, a neurologist and researcher at Mayo. Once development is complete, humans are wired for life, he said.
In part, nerves don't regrow because after an injury scar tissue seals off the ends. Windebank says it's probably a defensive mechanism to protect the nerve from further injury.
"But it causes more problems than it prevents," he said.
Until recent years, scientists believed that injury to the spinal cord would be permanent. But discoveries that led researchers deeper and deeper into the cellular behavior of neurons and to the molecules that unlocked latent growth potential are slowly opening the door.
"We found molecules that can keep the [nerve] cell alive and make it grow out again," said Martin Oudega, a biologist working with the Miami Project to Cure Paralysis at the University of Miami. He might collaborate with Windebank and Yaszemski.
Using some of those molecules, the Mayo researchers have launched a multifaceted attack to solve the complex problems nature has created.
First, they devised an implant to bridge the injury gap. Its a cylinder of biodegradable plastic with parallel tunnels. Over time it will dissolve as normal tissue replaces it.
Then they seed the implant with a variety of molecules to create what they hope will be the perfect growing environment for nerve ends. Some are cells taken from nerves elsewhere in the body because they encourage the myelin, the sheath that surrounds nerves, to grow. Other molecules inhibit the growth of scar tissue.
They are also experimenting with stem cells, the master cells that can be manipulated into becoming any kind of tissue.
All of this is done in the tiny backbones of rats. Humans, with their much larger spinal cords, would be much easier, Yaszemski said.
Reconnecting
So far, the researchers have shown that rat axons will grow into the conduit. Next, with the help of a $1.5 million grant from the National Institutes of Health, they hope to show that axons will grow all the way through the conduit to their partner nerves on the other side.
"So the green wire will connect with the green wire, and the red wire with the red wire," Windebank said.
Even if successful, would it help someone like Christopher Reeve?
Probably not, said Fehlings of the University of Toronto. Reeve suffered severe bruising of the spinal cord at the base of his neck, not a complete severing of it. Some of his nerves are intact, Fehling said, and it would not make sense to surgically sever the spinal cord to insert a bridge.
Researchers at the University of Toronto are working on a similar idea that might help people like Reeve, he said. They are using a ring seeded with growth-inducing molecules that would surround the injured spinal cord.
"That's a strategy that might work for a partial injury," he said.
Researchers elsewhere are taking different approaches, Fehling said. Some are looking for the gene or genes that instruct spinal cord nerves in fetuses to grow. If they could find a way to turn the gene or genes back on, then they could re-create nerve development in injured adults, he said.
In the end, paralysis might be reversed with any number of approaches, Oudega said. Finding them will be only a matter of time and money, he said.
Josephine Marcotty is atmarcotty@startribune.com.
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