With Reeve Drawing Spotlight, Spinal Cord Research Advances
Christopher Reeve puffs on a straw that drives his wheelchair that drives his life in the direction of hope. His celebrity and his determination to fight for patients with paralysis have taken him into some of the most prestigious spinal-cord research laboratories in the country. He knows well that his injury--he’s paralyzed from the shoulders down and requires a ventilator to breathe--was far too serious for him to qualify as a candidate in an experimental trial.
But the basic science that is helping animals walk has so stimulated his spirit that he can sit motionless in his state-of-the-art wheelchair, can wait 30 minutes for an assistant to bring a glass of juice to his lips to quench his thirst, can withstand wearing a tuxedo to breakfast so his staff doesn’t have to dress him more than once a day--because, he says, “there’s reason to believe.”
Reeve smiles. “The possibility of walking again is a practical problem that can and will be solved,” he says. “It’s a matter of time before scientists will get people moving again.”
The soft-spoken actor best known for his role as Superman in the hit movie series is now center stage in the race to find treatments for spinal cord injuries. His optimism has come to symbolize the excitement emanating from neuroscience laboratories throughout the world.
Last week, the National Institutes of Health announced that it would fund research using embryo stem cells, which can grow into almost any cell in the body. The research, which Reeve has supported, offers hope for spinal cord injury victims.
It faces a challenge, however, from critics opposed to using embryos as research material. They have vowed to block the move.
On other fronts, animals with spinal cord injuries are moving limbs again. So are a handful of patients undergoing an intense experimental exercise program at UCLA.
And there are a number of potentially revolutionary substances that could, when injected into the damaged spinal cord, promote the growth of new cells to restore communication between the brain and spinal cord.
Preparing for the Possibility of Walking
Reeve keeps himself in shape for that possibility--the day when treatments become a reality. “When the science is ready, we’ve got to be ready,” Reeve tells patients during visits to medical centers throughout the country.
He practices what he preaches. Every day, he wheels into his home gym, and his assistants lift up 190 pounds worth of Superman and place him into devices designed to keep his muscles stimulated and taut. His mantra is simple: “I always look as if I’m ready to stand.” And so it came as no surprise to friends and family when, in a commercial during the Super Bowl, Reeve appeared to stand.
But though his reality is far different, Reeve is changing the scope of the agenda for curing paralysis. Attention to the plight of spinal-cord injury patients is at an all-time high, and his speeches to Congress practically guarantee that money will be allocated for research.
The Problem Is Traced to Nerve Cells
More than 250,000 Americans live with paralysis caused by spinal cord injuries. Every year, 10,000 more are added to the roll. And the message for them has always been bleak: Doctors had nothing to offer. Why? The nerve cells that make up the spinal cord don’t grow and divide like cells outside the central nervous system. Once injured, always injured.
It was only 15 years ago that scientists began to coax nerve cells to grow with the help of “neurotrophic factors,” naturally occurring substances produced by the human body that regulate the development and growth of cells. At last there was reason to believe the spinal cord could heal.
“We’re learning that the circuits controlling movement and coordination are there,” said Dr. Gerald Fischbach, director of the National Institute for Neurological Disorders and Stroke in Bethesda, Md. “Now, we just have to figure out how to activate them.”
In test tubes and in animals, scientists are fixing the damaged axons--the long extensions of a nerve cell that travel from the brain to the cord and beyond to send messages. Others are even getting the axons to grow beyond the damage with the hope that the healthy extensions will reconnect to nerves on the other side of the cut.
The goal, says Fred Gage of the Salk Institute in La Jolla, is to figure out how to fix the internal phone lines so that the brain and spinal cord can communicate again.
The spine--made up of bony segments, or vertebrae--constantly talks to the brain to orchestrate movement, starting with such basic functions as breathing. At the site of a cut or bruise--called a lesion--the connection from the brain to the cord is disrupted. The brain may be sending signals, but the message won’t get beyond the cord.
Damage to specific vertebrae will lead to different levels of paralysis. Reeve’s injury is the most serious: damage to the highest areas, known as C1 and C2. Fewer than 10% of patients even survive such an injury.
Damage lower on the spine spares body functions controlled higher on the cord.
During the first days and weeks after an injury, the body sends out a signal from the immune system to contain the damage. But these chemicals are actually harmful to the injured axons, experts say, and can result in scar tissue and death of nerve cells in the region. Myelin, the coating around the axons that allows the sending of electrical messages throughout the body, is also damaged.
One focus of research is the slowing of this cell-damaging process--which would limit the extent of the injury. Doctors have been using the steroid methylprednisolone to reduce inflammation and block this chemical cascade. The medicine reduces patients’ inflammation by 20%, and researchers are testing more powerful drugs that might work better to limit the acute inflammation and damage.
Another tactic might be lowering body temperature during the acute phase of injury. And there’s evidence from animals that shutting down the immune system response early on could help contain the size of the lesion.
Gage of the Salk Institute has shown that adding neurotrophic growth factors at the time of injury can keep cells healthier. And he’s proven that damaged axons can regrow. “But how much is needed for functional recovery?” he asks. “And how do we get them to travel to the right places?”
Should the injured axons be saved, the next step is to restore the communication lines between the brain and the cord. “If we can restore these connections, we’d make major advances,” said Oswald Steward, a neuroscientist at UC Irvine.
There have been several obstacles. The first: A compound sends a message to the axon not to grow. Second: The scar that forms at the site of the injury makes it impossible for the axon, even if it could grow, to reconnect.
Dr. Martin Schwab, a scientist at the University of Zurich, first identified that inhibitory protein, termed Nogo, in 1989. Nogo is released by myelin and is considered an important key in nerve cell regeneration. Without Nogo around, nerve cells continue to grow and divide--and look healthy. Schwab and his colleagues have developed an antibody that blocks Nogo, and thus promotes cell growth.
But cell growth wouldn’t mean much if the axons weren’t making the right connection. So scientists are working to guide the axon to the right place. When axons are developing, they find their home naturally. But as the National Institute for Neurological Disorders and Stroke’s Arlene Chiu points out, “It’s another thing to ask an adult axon if it knows where to go.” And once the axon finds its target, it needs to form a synapse--a connection--with a neighboring cell.
Schwab and his colleagues have identified the human version of the Nogo gene and are developing a human antibody that would block the production of this inhibitory protein. Schwab said that the treated animals are able to move. Irvine’s Steward studies different mouse strains with varying amounts of wound-healing abilities. He has created a matrix of connective tissue, and finds that in certain strains of mice it can be used to fill the gap and draw the two ends of the broken spine closer together. Now he’s trying to make nerve fibers grow across the matrix and connect to nerves on the other side.
Doctors believe that it will only be a matter of time before they can bridge the cut spinal cord with nerve cells. Mary Bunge and her colleagues at the Miami Project to Cure Paralysis, part of the University of Miami School of Medicine, are working on just that. First, they remove peripheral nerve cells, called Schwann cells, from the leg and let them multiply in a test tube. These Schwann cells normally make myelin.
In the animals’ spines, they place millions of these cells in a small casing, lay it across the lesion and add growth factors. Indeed, the axons grow and make connections outside of the lesion, Bunge said. The Miami researchers have discovered that cells that line the nose also can work as chaperons to guide the axons to their right target, and studies are underway to test these particular cells as possible treatments.
At UCLA, exercise physiologist Reggie Edgerton has evidence that the spinal cord has its own internal memory programs that drive movement independent of the brain. The proof comes from experiments conducted there on animals that have undergone a complete spinal cord cut--and that have been trained to walk, or at least stand.
Such a learning mechanism independent of the brain had not been envisioned. But when Edgerton began his experiments, he saw that a significant amount of motor “learning” was being done by the spinal cord itself.
In Edgerton’s studies, an injured animal lifts a foot, then puts it down. If Edgerton puts a rod in its path, the animal anticipates “and will lift its foot higher.”
“There’s no connection to the brain,” he said. “The system is doing what it needs to do when it matters. The spinal cord can learn. We just have to figure out how to teach it.”
Edgerton began putting some patients on a modified treadmill--even Reeve. Paralyzed patients are placed in a suspended harness, and therapists move the patient’s limbs in a stepping motion.
Edgerton and his colleagues have put 15 people through the 12-week exercise training. The findings have led to a large clinical trial--300 patients at six centers. Patients in the trial will undergo three months of exercise and then be tested to see if walking improved their spinal cords.
“In humans, we can’t get them stepping completely and independently, but close to it,” Edgerton said. “There was one young man who doctors said would never stand again. Now, he walks with a cane. I am confident that there are a lot of people in wheelchairs who need not be.”
At his home, Reeve works out daily. He rides a stationary bicycle with the help of electrodes taped to his legs that send stimulation to the muscles to move the pedals. His assistants strap him onto a bench that is then tilted into a vertical position to keep his body erect and his weight-bearing muscles active. “Recovery will go to the fittest,” Reeve said.
Learning to Move With High-Tech Help
High-tech electrical devices are also helping patients walk again. At the University of Miami, Lucilia Aguilar uses a walker to move from one end of the rehab laboratory to the other. An architect, Aguilar was paralyzed from the waist down after part of a house structure fell on her. Now Aguilar is one of dozens of patients learning to use these devices. She can’t feel her legs, but she can move them for the first time in six years.
Researchers in Belgium recently announced they had surgically placed 15 electrodes in the nerves and muscles of a paralyzed man’s legs, connecting them to a computer chip inside his abdomen. In the same way Aguilar uses buttons on her walker to send an electrical pulse through her electrodes, this 39-year-old financial consultant from France gets his walking signals from scientists controlling the computer program.
Scientists expect a mix of approaches ultimately will help people regain function.
For Reeve, the more attention and money he can help generate, the sooner he believes the cure will come. In his nightly dreams, he is always moving--never disabled. Since Reeve’s 1995 accident, the spinal cord at the level of the injury--the second cervical vertebrae--has shrunk to one-quarter of its normal size. The cut on the first cervical vertebrae was 20 millimeters long. The spinal cord above and below the damage is healthy.
Now he has feeling at the base of his spine. He can move his shoulder blades, and he can stay off his ventilator for a few hours at a time. And when it would be so easy to shut himself off from the world, he travels state to state talking about the research. It’s the biggest role of his life. “Twenty-eight years as an actor really helps,” he said. “Over that time, I’ve been rejected but still had to believe in myself. As an actor, you need discipline and work long hours. And then you go on stage and give it your all. I don’t compete with actors, but I compete with myself and my machines every moment of my life.”
