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For Mayo scientist, spinal-injury research is personal

November 24, 2018

Peter Grahn has faced the same question for a dozen years since he dived as a reckless teen into a southwest Minnesota lake, slammed headfirst into the shallow bottom, and floated — face down and motionless — on the surface.

Will I ever walk again?

Turns out, he might end up as one of the first researchers in the world who can really answer it.

The accident left Grahn with quadriplegia at 18 but, fueled by the lack of research at the time, he turned his life’s focus toward rehabilitative medicine and eventually became a spinal cord injury researcher at Mayo Clinic.

The pursuit yielded results in September, when Grahn and his Mayo colleagues published a globally recognized breakthrough: using electrical stimulation and therapy exercises to help a paralyzed man walk the approximate length of a football field.

“I still recall, early on after my injury, asking some of the medical people helping me, ‘Why does the spinal cord not recover or heal itself like a normal injury to your skin or something?’ ” Grahn said. “They gave me basic answers that I could understand, but they also said it’s not totally understood. That sparked my interest.”

Now Grahn is among a small but growing international group of spinal cord researchers who are posting results in medical journals at a rapid pace, testing what were thought to be the limits of spinal cord regeneration.

They are challenging the notion of a “complete” spinal cord injury, which means no recovery is possible. They’re also exploring the possibility that recovery doesn’t really plateau, as previously thought, and that healing is possible even years after an injury.

“Research is suggesting that, no matter how far out the injury was, it doesn’t seem to matter,” Grahn said.

Initially, the Mayo researchers set out to replicate a Kentucky study showing that electrical stimulation could help people move paralyzed limbs. They implanted a stimulator in a Wisconsin man who suffered a severe spinal cord injury in a snowmobile accident.

The Medtronic device was federally approved to manage pain, not coax movement. But over time, the stimulation helped the man move his legs, then sit up, then stand, and eventually take multiple steps with the help of a walker.

The study, published in the journal Nature Medicine, pushed the team’s ambitions beyond their initial goals.

“It was like, ‘OK, so now that we did this, what’s the next step, right?’ ” Grahn said.

If the mood among spinal cord researchers is one of unbounded optimism, Grahn tempers that with the reality of his own experience, saying hopes shouldn’t get too far ahead of actual results. He has sensation in his legs but can’t move them, so he moves around in a wheelchair. He can move his arms, but not his hands and fingers.

“I’ve been through enough of these — when these news pieces come out [promising cures] and then five years later it’s just five years down the road,” he said. “I’m sensitive to the issues of giving false hope to the spinal cord community, even though hope is necessary.”

Big dive, shallow lake

Grahn was a high school graduate in the summer of 2005, looking ahead to studying and playing basketball in college, when he went to a lake cabin near Willmar.

He was tossing a football with friends and feeling careless when he charged down the dock and dived into what the 6-footer didn’t realize was only 2 feet of water. The instant he hit the surface, he knew it was bad. Friends rolled him over so he could breathe, and a paramedic nearby raced to help.

After being flown to St. Cloud for intensive care and surgery to fuse his fractured vertebrae, Grahn went to a physical rehabilitation center in the Twin Cities. An athlete, he figured he would recover much as he had after other injuries. But after months of work, he grew depressed over the apparent permanency of his injury. Family support helped him move forward.

“Dwelling on it wasn’t going to help,” he said.

Grahn enrolled at Southwest Minnesota State University a year after the accident. He had been interested in rehabilitation medicine before, but the injury gave him a new focus.

A Mayo physician, Dr. Anthony Windebank, hired Grahn to work in his lab, which focused on tissue and spinal cord regeneration. Grahn eventually earned a doctorate in neuroscience and joined the lab full time in 2016.

Quite apart from his research skills, colleagues say, Grahn brings the advantage of his personal experience, which allows him to communicate with paralyzed patients and appreciate their struggles.

“He has the ability to relate to them more than any of us,” said Megan Gill, a physical therapist who worked with the paralyzed research subjects and co-authored the Nature Medicine paper.

Gill has her own inspiration story — a bloodstream infection left her without use of her left leg for much of her senior high school year and with lingering nerve damage today.

Gill said the Mayo advances are exciting but still leave many questions unanswered. Nerve stimulation in paralyzed patients takes advantage of dormant but intact tissue at the site of their spinal cord injuries. But researchers don’t really know how it works, or whether it is forging new connections that travel all the way from the paralyzed limbs to the brain.

And for now, everything remains experimental. “I can’t offer it to my patients tomorrow,” she said. “It’s hard.”

Swiss competition

One challenge of spinal cord research today is keeping pace with new discoveries and competitors. When Grahn and his colleagues published their study on the patient who was able to walk, it came out on the same day as a similar study in the New England Journal of Medicine by researchers at the University of Louisville.

“Our initial reaction was, ‘This is kind of a bummer,’ ” Grahn recalled with a laugh.

The Swiss researchers reported using a modified version of their Medtronic implant to provide pulses, rather than continuous stimulation. They had worked with patients who had some mobility, or at least some nerve signals, in their paralyzed limbs, whereas the Mayo and Louis­ville patients had no such nerve signals. But their results went a step further, allowing patients to walk even when the implant was shut off.

The combined results from competing centers has observers making bold predictions.

“We should consider these results across three independent research groups as a breakthrough in the treatment of paralysis,” read an editorial accompanying the Swiss research. “The field of spinal cord injury is poised to take a giant leap forward in the treatment of what was until very recently considered incurable: paralysis.”

Mayo’s lab is something of an upstart compared to some of its competitors. Its research with that first patient, and work with a second whose results haven’t yet been published, was cobbled together with federal and state grants and support from groups such as the Jack Jablonski Bel13ve in Miracles Foundation, named after the former Benilde-St. Margaret’s high school hockey player who was paralyzed in a game in 2011.

Grahn said they are now seeking additional funding to expand on their work. Having so many of the world’s top doctors on site gives the lab a big advantage, he said.

Despite his life-changing accident, Grahn said he considers himself fortunate, with an exciting career, a wife and children. He allows himself the dream of walking, but he knows how much work remains before stimulation combined with therapy can be offered clinically to patients.

“I know,” he said, “what we don’t know.”

Jeremy Olson • 612-673-7744

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