A Breakthrough at Last for Spinal-Cord-Injury Research?

On Tuesday, the FDA granted approval for a first ever human trial of cellular transplant to cure paralysis

  • Share
  • Read Later
Andrew H. Walker / Getty Images for The Buoniconti Fund

Marc Buoniconti on September 26, 2011, in New York City

In the early winter of 1988, I traveled to Miami to visit Marc Buoniconti. He was 24 years old at the time, and in many ways looked quite fit — full of energy, chattering on about his plans, exactly what you’d expect from a person his age. But Buoniconti wasn’t fit. He was in a wheelchair and hadn’t moved a muscle below his shoulders since fracturing his spine between the third and fourth cervical vertebrae in a college football game in October 1985.

By the time I met him, he had already done the grueling work of weaning himself from his respirator — training new muscles and learning new techniques to breathe on his own. And that freedom allowed him to assume the job of point man for the Miami Project to Cure Paralysis, an organization co-founded by Buoniconti; his father, NFL Hall of Famer Nick Buoniconti; the University of Miami; and a handful of local surgeons.

“I was never in denial about my injury,” Marc Buoniconti told me at the time. “When you can’t move, you move through that phase pretty fast.” But the absence of denial did not mean the absence of hope. Buoniconti was adamant that he would dedicate his life to getting out of his chair and helping the 300,000 other Americans living with spinal-cord injury do the same. In the meantime, he’d keep himself as fit as possible. “When the cure comes,” he said, “I plan to be ready.”

Buoniconti is now a 45-year-old man with a degree in psychology, still with the Miami Project — and still in a wheelchair. But the cure he spoke of 27 years ago just got a very big step closer. On Tuesday morning, Miami Project doctors convened a press conference to announce that the U.S. Food and Drug Administration (FDA) had just granted them a green light to begin Phase 1 human trials for a new surgical technique in which nerve cells from the leg would be transplanted to the spine of newly paralyzed patients in the hope that they would grow — restoring at least some function and sensation.

“I am more optimistic now than I have ever been,” says Buoniconti. He has reason to be.

What makes spinal-cord injuries as devastating as they are is that everything about them plays out in absolutes: they are instantaneous, utterly disabling and horribly permanent. That last fact has always presented both a puzzle and an opportunity. Nerves in the peripheral nervous system (PNS) — those that carry signals in an arm or leg, say — are able to regenerate after injury. That’s why you can badly lacerate a finger and retain full use of it. The central nervous system (CNS) is a different matter. An injured spine remains an injured spine, period. Find and harness what it is that makes things so different in the PNS and you just might get a wounded spine to heal.

As researchers learned, there are a lot of things that drive peripheral regrowth, but perhaps the most important are known as Schwann cells, which are not nerve cells themselves but a kind of attendant, helping neurons regrow myelin — the fatty insulation that covers nerve strands — and otherwise stay healthy and functioning. For some years, Miami Project scientists have been transplanting Schwann cells from the legs of paralyzed rats, mice, pigs and primates to the site of the spinal injury and have been astonished at the results: in many cases, the animals recovered 70% of the lost sensation and function. That is exactly 70% more than most spinal injured patients have been told to hope for.

What the FDA is permitting — and what the Miami Project announced today — is preliminary, or Phase I, trials of Schwann cell transplants in humans. Under the new study, researchers will seek eight volunteers with fresh spinal injury at the thoracic level — farther down the spine than the neck, at a point at which damage can lead to paraplegia rather than quadriplegia. Schwann cells will then be harvested from each patient’s leg, grown and purified in petri dishes for 26 to 40 days, and transplanted into the spine. The patients will be followed for at least a year to determine what, if any improvement they’ve experienced, or what, if any, problems they’ve encountered.

This is by no means a no-risk decision for the volunteers. Since their own Schwann cells will be used in the transplants, there won’t be any risk of rejection. In that sense, they’ll behave like self-harvested stem cells. But as with brain injury, it’s often impossible to determine who will show improvement in the first year, who won’t and what it is that makes the difference. For many spinal patients, at least some function can return naturally as cord swelling subsides and the spine stabilizes, and the newly injured may not want to mess with their chances of improvement by volunteering for something that’s never been tried before. But it’s not an option to wait a year or two before volunteering for a Schwann trial either, since the window for improvement can close quickly.

All of these risks and potential benefits will be discussed with volunteers before they are accepted into the trial, but all of that is for tomorrow. Today, the Miami researchers are simply thrilled that they’ve gotten this far. “We believe today’s announcement is just as important to our field as man’s first step on the moon was to the space program,” said neurosurgeon and project co-founder Barth Green. “When we started the Miami Project, the short-term goal was to improve the quality of life of people living with paralysis, but the long-term goal remains re-establishing function and finding a cure.”

Buoniconti, the ex-jock, still believes he could be one of the beneficiaries of that cure. “Always in the back of my mind, I’m an athlete,” he says, “and have to prepare for the future.” In a small but profound way, that future may just have changed.