Time for a cure?

Local victims of spinal cord injuries fight to bring research to human trials

BY ANNE QUINN

"Oh, to be a rat," actor-director Christopher Reeve once said. He was referring to researchers’ common use of rodents for experiments that they refuse to try on people. Reeve, the handsome, beloved actor known to millions as Superman, became spokesperson for the 250,000 Americans with spinal cord injuries after his spinal cord snapped when he fell off a horse in 1995. The accident left him paralyzed from the neck down and unable to breathe independently. The Christopher Reeve Paralysis Foundation, created from a merger of the American Paralysis Association and the Christopher Reeve Foundation, donated $4.8 million to spinal cord injury research in 1999, according to its annual report.

Reeve's rat envy is shared by people in a SLO County group called SCI Research Advancement who believe the world's best-known SCI victim may be ready to hear what they have to say.

The 50 SCI Research Advancement members want researchers to bring their work to human trials. They believe that the time is right for technology to release them from their dependence on wheelchairs, but that researchers are stalling in order to keep money that celebrities like Reeve bring flowing into their labs. It's a game of politics and money, they assert.

"Researchers look for a cure [and fame and a Nobel Prize], and, in their search for a cure, bypass potential treatments," said SCI Research member and former state assemblyman Tom Bordonaro Jr.

"Reeve's accident effectively doubled the amount of money coming into SCI research," added Will Ambler, who founded SCI Research Advancement. "But at the same time the interval between lab research to application has also doubled."

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Ambler, 32, is a former soccer coach and baseball player who became paralyzed from the waist down in a near-fatal motorcycle accident in 1992. "How would you like to go to the hospital thinking they are going to do something and they say they can do zero? This wheelchair is my gift from the medical community," he said bitterly.

Immediately after his accident, Ambler began tracking developments in SCI research. "In 1992, I was told by the premier researchers in the field that there would be a cure for SCI by the end of the decade," he said. "At the time, that was an unbearable thought–it seemed so far away," Ambler said.

Through the American Paralysis Association (since merged with the Christopher Reeve Foundation), Ambler discovered the work of Mark H. Tuszynski, M.D., Ph. D., at the University of California, San Diego. He became his biggest fan.

Since 1991, Tuszynski has been involved in developments in gene therapy, and specifically a technique that uses cells that have been genetically altered to produce nerve growth factor, a naturally occurring substance. Like telephone wires, fibers called axons are vital for transmitting messages to and from neurons within the brain.

Half of Tuszinski’s research is devoted to work on the spinal cord, which, if the axons carry the right messages to the brain, could help the injured walk again. The other half is devoted to using gene therapy to restore human brain cells. This research is being conducted in hopes of delaying the onset of Alzheimer’s disease.

Funding for Tuszynski’s research comes from a variety of sources–the federal government, private organizations like the American Paralysis Association, and individuals like Ambler.

"In 1992, when I first got a hold of Tuszynski, I was told

human trials would begin in 1993," Ambler said. "Next I was told it would be September, 1994. Then, 1995. At that time, I was fund-raising for him. I know he got a half-million dollars that year, because I was in the loop."

In rat studies in 1997, Tuszynski tried gene therapy to stimulate the regrowth of damaged axons along the spinal cord by changing the function of injured animals’ cells and allowing them to produce growth factor directly at the site of injury. The result was that the rats could partially walk again.

In November, 1997, Tuszynski wrote a letter to a donor Ambler had persuaded to send the neuroscientist $50,000. Tuszynski described the letter as "a progress report" on the first round of experiments in gene therapy in primates. Tuszynski called the experiments a success. "These findings indicate that gene therapy in the primate can support the robust growth of the spinal cord," the letter read.

Ambler was thrilled that Tuszynski was beginning to use gene therapy with primates. It meant the next step was to try the procedure out on humans. He was delighted by Tuszynski’s description of "robust growth." The letter contained more good news: "Genetically modified cell implants, axons from the spinal cord, grew extensively into the transplants," it said.

Ambler wanted to be Tuszynski’s first subject. He expected a call any minute. It never came.

In May, 1999, Congresswoman Lois Capps wrote John Alksne, Dean of the School of Medicine and Vice Chancellor for Health Sciences at the University of California, San Diego, and asked that Ambler be considered as a subject for Tuszynski’s experiments. In June, Governor Gray Davis wrote a similar letter.

Both letters were answered in July, 1999, by Sara Steinhoffer, manager of UCSD Advocacy Programs. "In fact, you are mistaken in your belief that primate spinal cord injury trials have been conducted for the specific application of this research. Accordingly, we are several years away from human trials," she wrote. The university claims the therapy was tried only in rats, not primates, even though Tuszynski had mentioned gene therapy experiments in primates both in his letter to the donor and in a videotaped interview by SCI Research Advancement.

Ambler thinks that the school and the researcher are lying. He says Tuszynski's letter to the donor describing the success of gene therapy in primate spinal cords–a letter written nearly two years earlier–proves that human trials could be going forward.

Ambler said that his research also found that in 1911, one J.F. Tello reported a discovery similar to Tuszynski’s. While science is by nature cumulative, it nonetheless struck Amber that after nearly a century researchers are no closer to human trials.

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Ambler doesn’t want this research just so he can walk again. There are a host of other maladies that affect an SCI individual, he said.

"People look at a person in a wheelchair and say, ‘how horrible, he has lost the use of his legs,’ but that is the least of my concerns," said the former SLO High School soccer coach. "I have constant pain. I can take drugs, but I choose not to. The higher up the injury, the more functions you lose. Christopher Reeve can't breathe. Tom Price and Tom Bordonaro [other SCI Research Advancement members] can't perspire, or tolerate any heat–hot temperatures will begin killing their brain cells. Most SCI individuals no longer have sexual function, or control of bowel and bladder.

"Most people don't know that we're all on a bowel program, meaning we use suppositories and other methods so that we can regulate our bowel movements and avoid accidents when we are in public. No one ever talks about that. I once saw an interview with Christopher Reeve that came close. When the interviewer asked him about it, I was waiting for him to explain the bowel program by saying it is to make sure I don't shit all over myself when I'm up here on stage–but of course he didn't," he said.

Ambler no longer looks to Tuszynski for relief.

On Feb. 12, Tuszynski’s office issued a press release announcing the beginning of human trials on gene therapy research for Alzheimer’s disease. The 50 members of SCI Research Advancement are furious.

"If it is safe to inject genetically modified cells directly into the brain, then it is also safe to place them in the spinal cord," argued Bordonaro, who has been in a wheelchair since he was an 18- year-old Cal Poly student and a passenger in a car accident on Cuesta Grade.

"We wanted access to that research, we wanted to start human trials. When Tuszynski announced he would be starting human trials for Alzheimer's patients, that was the straw that broke the camel's back," said Al Price, whose son, Tom, had his spinal cord crushed by a motocross bike in his back yard in 1997.

But Tuszynski argues that it’s not safe to test gene therapy in spinal cord patients, and that gene therapy in Alzheimer’s disease is easier than in spinal cord injuries.

"The challenges of axonal regeneration in the primate spinal cord are, in fact, more difficult than what we are attempting to accomplish in the brain," he said. "In the brain we try to prevent cell loss [as, for example, in Alzheimer's disease], and if we intervene early enough and are successful then we do not have to reconstruct circuits because they will be ‘rescued’ before they have extensively degenerated."

However, in spinal cord injuries, doctors have to try to reconstruct complex circuits that have already been damaged. "Further, we have found a bridge that many different types of axons will grow into at a site of injury, and then grow out of again to find their appropriate targets, which may be a long distance from the injury site," Tuszynski explained. "In the spinal cord we must find a bridge for some, but not all, axons. One of the types that we have not yet found a good bridge for is the type of axon that controls motor function [movement]."

Tuszynski also said that the only types of axons that respond to growth factor gene therapy in the spinal cord are sensory axons–those that transmit sensations like pain. That makes experiments on humans too dangerous–and too painful–at this juncture.

SCI Research Advancement members also believe that experiments in treatment for Alzheimer's disease, if successful,

would have wider application and thus be of more interest to the

pharmaceutical industry than would similar advances in treating spinal cord injuries.

Alzheimer's is the most common neurodegenerative disorder, affecting 4 million people, according to the Alzheimer's Disease Education and Referral website (www.alzheimers.org). Tuszynski's research likely offers not a cure for Alzheimer’s disease but rather a postponement of the onset of the disease. Delaying the disease could save the medical industry almost $10 billion dollars over a decade, according to the American Journal of Public Health.

Unquestionably a method for delaying Alzheimer’s Disease will appeal to a wider market, but other factors may be influencing the direction of Tuszynski’s research.

Research application is regulated by the FDA, an agency that discovered in the 1950s that caution pays. In the 1950s, the agency was under fire for not approving Thalidomide, a sedative prescribed for pregnant women to help them sleep. A plucky FDA researcher, Frances Kelsey, was under pressure by American pharmaceutical companies to approve the drug, which was already popular in Canada and Europe. Then the evidence came in: 12,000 babies whose pregnant mothers had taken Thalidomide were born with deformed or missing limbs and other severe defects.

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SCI Research Advancement chipped in $250 to buy Bordonaro a seat at a glitzy fund-raiser for the Rehabilitation Institute of Santa Barbara at the Fess Parker Doubletree Resort on Feb. 7. Reeve was guest of honor.

The hope was that Bordonaro, an experienced politician, could find a way to speak to Reeve for just a second. Besides, he was the only SCI Research Advancement member who owned a tux.

The group became Bordonaro’s first client when he opened his now-defunct public relations agency. Ambler said the organization has paid the ex-state assemblyman $2,000 all told.

They sent with Bordonaro a package that included a video and documentation detailing what they believe about the research community in general and about Tuszynski in particular.

If Reeve became interested, the group hoped, the tape would make it onto television shows like 60 Minutes or 20/20, owing to Reeve's access to the scientific community and media connections.

"I was able to ask a question during the question and answer period following Reeve's speech," Bordonaro said. "I told him a little about our group and got the packet to him. He agreed with us 100 percent. He said that researchers need to get out from behind the microscope, visit rehabilitation centers, and talk to people."

Although Reeves appeared to agree, its not clear the group will succeed in calling Tuszynski’s work into question. He is one of the country’s most respected neuroscientists, and he holds a seat on the Christopher Reeve Paralysis Foundation’s Science Advisory Board.

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Bill Walther, a resident of Arroyo Grande who was injured in a motorcycle accident 15 years ago, does not share SCI Research Advancement members’ cynicism about research scientists, but he does think that the lack of progress in SCI research is about politics and money.

"If the government spent on SCI research what they spend on one military submarine that it doesn't need or want, it would give me the chance to walk," he said.

Walther was speaking at a meeting of SLOCO Access, a nonprofit disability awareness and advocacy organization serving SLO County that was begun in 1995 by Flicka Dukes and Cherie Fitch.

At the meeting Walter shouted out, "Listen everybody, there are basically two factions in the SLO County disabled community. SCI Research, Will Ambler's group, that is fighting the research community, and SLOCO Access. What side are you on?"

Fitch, who has multiple sclerosis, said, "When I was diagnosed, in 1984, they said [a cure would be discovered in] 10 years. If they had an unlimited budget they would do it, I am sure."

SLOCO Access member Robert Tidalgo said, "I agree with Ambler. There's a lot of money in this whole situation–money and greed."

Mike Ward, a former SLO City Fire Captain who was injured in a

bicycle accident in 1997, said, "I'm convinced there are some people out there who are dedicated, and I believe they are close."

Ward came to the meeting with his hand in a cast. He just returned from Stanford University Hospital where surgeons placed eight electrodes into his hand. There is a corresponding implant in his chest, and wires connecting the devices. He also said there is a "joystick" in his left shoulder. "This is to restore movement in my hand," he said. "For three years now, I haven't had use of my fingers. This is going to be big."

The SLOCO Access meeting was the last regular meeting of the organization before its big annual event, the daylong Abilities Expo, coming on Friday, March 9. Fifty exhibitors will gather in the SLO Veterans Memorial building on Grand Avenue to show products and services designed to make life easier for disabled people–everything from voice-recognition programs to mobility aids.

"SLOCO Access presents positive attitudes and works toward cost-effective solutions for compliance with the Americans with Disabilities Act. I know there are still negative attitudes toward people with disabilities and physical barriers in SLO County, but I believe SLOCO Access is a guiding light toward our futures," said Dukes.

A sign at the SLOCO Access office reads, "Attitudes are the real disability."

Dukes said she met Ambler early in his fight for human trials. "I think Will Ambler is an extremely intelligent young man," she said. "I am happy to have him push for a cure for SCI. I also see 'cure' and ‘accessibility’ existing peacefully together."

Meanwhile, SCI Research Advancement is focusing its efforts on getting research out of the lab and into the hands of physicians and surgeons. Price said the group is working with a highly respected neurosurgeon in Denver who is interested in human trials. They are also watching Michal Schwartz, a professor at the Weizmann Institute in Israel, who is starting human trials in acute SCI patients.

"I’m not going to hold my breath for a cure," Walther said.

"Sometimes I think you need to accept things. Everybody goes through anger, denial. Acceptance is another step in the process too." Æ

New Times reporter Anne Quinn can be reached via e-mail with ideas and comments at [email protected].