Nerve-Regrowth Studies Buoy the Paralyzed

Bob Yant thought it could never happen to him.

Living on Balboa Peninsula so close to the Wedge, he had heard the ambulance sirens each time yet another surfer cracked his back or neck and ended up paralyzed for life. He knew the risks as he sauntered down to the beach every day that summer of 1981, but, like most of us, he didn’t think about them.

Then the “meat wagon” came for him.

Diving into a breaking wave, Yant struck his head on a sand bar. Instantly paralyzed from the shoulders down, he was catapulted overnight from the idyllic life of a healthy, 30-year-old surfer to a world where showering and shaving is a two-hour chore and brushing his teeth is an accomplishment. Like hundreds of thousands before him, Yant heard a doctor utter those awful words: “You’ll never walk again.”

“When they first told me I was going to be a quad, oh, man, I cried,” Yant recalled, sitting in his comfortable one-story Balboa home, describing the events with a detachment born of spending five years in a wheelchair.

But he is hardly detached about discoveries made in spinal cord research that might--just might--enable him to walk again.

‘Wisdom’ Falling Away

When Yant, founder and president of the American Paralysis Assn.’s Orange County chapter, became a quadriplegic five years ago, the world still accepted the old medical “wisdom” that central nerve tissue could not regenerate, that a paralysis like Yant’s was incurable.

Now researchers have proved that nerve cells will regrow under the right circumstances, and indeed, that a cure for spinal injuries may not be many years away.

Some recent developments:

- At UC San Francisco last month, researchers began testing in humans a drug they think will, if injected shortly after spinal cord injury, actually prevent paralysis in many cases.

- At UC Irvine and San Diego, scientists are working on regenerating damaged central nerve tissue in rats--a process called axon sprouting--by using certain hormones or by transplanting healthy tissue from aborted rat fetuses or from other areas of the animals’ bodies.

- At Yale University last fall, two scientists severed the spinal cords of sea lampreys, eel-like creatures with nerve cells similar to those of humans, and only a few months later, some of them were swimming again. This was the first evidence of spinal cord regeneration in a vertebrate; now, using a special dye technique, the researchers hope to unlock the lampreys’ secret.

- In other labs across the country, doctors and scientists are collecting clues about what makes the central nervous system work in the first place.

The central nervous system operates like the telephone network of a big corporation. The brain decides what muscles will do and “phones” its various “offices” with its orders.

The thin, gelatinous spinal cord--about the width of a little finger--is the telephone cable, carrying electric impulses from the brain to nerves that control muscles throughout the body. Break the connection and the brain has no way to control its various parts. The result is paralysis.

Most injuries to the spinal cord are relatively minor bruise-like abrasions. But unlike most other body cells, central nerve tissue does not regenerate by itself, and even a small injury can cause paraplegia (loss of sensation below the waist) or quadriplegia (below the shoulders or neck).

In 1906, Santiago Ramon y Cajal, a leading neurologist, won a Nobel Prize in part for determining that central nerve tissue could not be regenerated--a thesis taken as gospel until very recently.

Before World War II and antibiotics, there wasn’t much need to challenge the assumption, since infections killed most spinal cord victims. Today, however, about 500,000 Americans suffer from some form of paralysis. Each year, there are as many as 15,000 new victims--average age 19. That’s a new victim every 30 minutes.

One hope lies with Dr. Carl Cotman, a researcher at UC Irvine and a past winner of the MacArthur Foundation “genius” grant.

Dogma Turned Around

“It was said just three years ago that a nerve fiber in the central nervous system wouldn’t regenerate. Period. That was dogma,” Cotman says. “But that’s clearly now been turned around. You can make a nerve fiber regenerate.”

Cotman is concentrating on two areas:

- Transplanting nerve tissue from rat fetuses into the damaged area of a rat’s spinal cord and watching to see if the regrown axons (the long tentacles that carry electric impulses from one nerve cell to another) will rewire the circuitry.

- Exploring natural chemicals in the body--called growth factors--to find out how they affect the natural healing process.

One of the major stumbling blocks, Cotman said, is the body’s own survival instinct. When a spinal cord is damaged, the nervous system automatically seals itself off within a few days, creating a barrier of gliel cells, which prevents toxins and bacteria from infecting the wound. But in the process, the newly erected wall also prevents growth factors from helping out and deflects any regrown axons.

Body’s Timing Is Off

“We think one of the real problems is the timing is off,” Cotman said. “The brain has a way of establishing priorities and healing itself. The first thing it does (after an injury) is say, ‘Here come the bacteria, here come the toxins, let’s seal the whole thing off.’ If you don’t do that you lose the whole animal or the whole person. . . .

“We think some of those mechanisms have to be mobilized at the expense of some growth. After that’s done, then the growth starts, but by then it’s almost too late.”

However, Cotman’s studies have shown that gliel cells have healing powers of their own. In experiments, he transplanted some cells to an injured rat’s brain and discovered that they minimized secondary cell death and even accelerated the healing process a little by secreting their own growth factors.

The trick will be discovering and reproducing those chemicals.

Silvio Varon, a biology professor and researcher at UC San Diego’s medical school, is one of dozens of scientists working on that.

‘Very Large Problem’

“Under usual circumstances, nerves that are damaged will not regenerate, but that does not mean that they cannot ,” said Varon, who is investigating neuronotrophic factors, chemicals that promote nerve cell survival. “That shifts the problem to: Under what circumstances will they? That, of course, is a very large problem.”

Regenerating the nerve cells is not enough by itself, he said. That’s just one step in a long, involved process.

A doctor must first keep the damaged neurons alive, a process that apparently includes fighting the body’s own protective functions. Then the neurons--or nerve cells--must be coaxed into growing new axons.

That is the step scientists are working on. After getting the axons to regrow, doctors must be able to guide them and then hope that their “partner cells,” the receptors on the other end, are still alive and capable of hooking up with the axons.

Meanwhile, other researchers have been concentrating on the “acute” period of spinal cord injury, the first few hours or days when paralysis can best be prevented. Scientists know that much of the damage a spinal cord victim suffers comes from massive nerve cell death in the days after the accident.

If doctors can prevent the secondary damage, paralysis can be avoided in many cases.

UC San Francisco neurologist Alan I. Faden began testing in humans last month a hormone that has prevented or minimized paralysis in nearly all of the animal test cases conducted over the last few years.

Eight years ago, Faden and another doctor discovered that endorphins, the body’s natural painkillers, actually cause damage in spinal cord cases, often resulting in paralysis. Faden’s new compound is a synthetic analog of thyrotropin-releasing hormone (TRH), a natural body substance, and is supposed to block the damaging effects of the endorphins without dampening their pain relief.

“Theoretically, it appears to be an ideal drug to use,” said Faden. “Most of the (test) animals appeared to be entirely normal, even after severe injury. Not only were they walking, but they were climbing and running and everything.”

Commercial Interest

Several drug companies have taken an interest in TRH and if the current round of testing is successful, Faden estimates it could be available commercially within the next several years. And because it appears to have no negative side effects, it could be administered by paramedics as a “just in case” measure.

Faden says his field has reached this “attitudinal turning point,” and even though much of the work is still in its infancy, the limited successes have generated much enthusiasm. Unfortunately, most of it has been limited to researchers and fund-raisers.

Most doctors still tell new victims they will never walk again, either out of ignorance or a fear of producing false hope, experts say. And government agencies, major trusts and insurance companies have yet to funnel much money toward research.

“It’s the old view--I mean, why spend money on something that’s hopeless?” explained Joseph Alioto, son of the former San Francisco mayor, who became a director of the American Paralysis Assn. after his 12-year-old daughter Michaela was paralyzed in a skiing accident.

“It’s so absurd to believe that we’re not going to be able to ever reverse paralysis. Why, we couldn’t even touch the heart 15 years ago. Today, we’re doing bypasses every day and putting in artificial hearts. It’s the old ‘the world is flat’ idea.”

Not Enough Support

Retired Rear Adm. M.D. Van Orden, once chief of research for the Navy who retired to direct research for the American Paralysis Assn., agrees that private businesses are operating under worn-out misconceptions.

“Unfortunately, we’re not getting a great deal of support (in the form of research funds) from the insurance companies,” he said. “They still feel that this is something that’s purely experimental. They don’t see that this investment will help them.”

Association officers and researchers point out that economics should push the country into making a cure for spinal injury a national priority. The government spends about $4 billion a year on medical costs and welfare to quadriplegics and paraplegics, and the paralysis association estimates that the economy loses another $4.5 billion in lost wages and productivity from disabled people who are considered unemployable.

The National Institutes of Health says the government spends about $20 million a year on research into spinal cord injury and regeneration.

Researchers also point out that much of the knowledge gained from their work also has applications for victims of stroke, brain damage and Alzheimer’s disease.

There are still major obstacles, of course. Researchers haven’t established that the nerve cells, once regrown, will be able to form useful connections.

“(We’ve taken) a big step, but only a step,” said Richard L. Sidman, a Harvard scientist studying peripheral nerves and what makes them regenerate. “That’s a big deal for the researcher, but not a big deal for the patient yet.”

But even though researchers are cautious about making predictions, many are excited and optimistic about the chances of curing spinal cord injury.

Meanwhile, people like Bob Yant continue plugging away, trying to provide scientists with the money they need. Yant organizes meetings and lectures, solicits funds, counsels newly paralyzed patients and even uses splints attached to his fingers to type up a bimonthly newsletter on his home computer.