Pharmaceutical Executive

Neurology's Broader Promise: An exclusive Interview with Christopher Reeve.
Author/s: Wayne Koberstein

It could happen to anyone.

That is the resounding message that comes through in a quiet conversation with actor and health activist Christopher Reeve. In an instant, even humanity's highest and mightiest can lose the mobility they have always taken for granted. Be it by sudden accident or slow disease, anyone may suffer a major disruption to the human nervous system that severs feeling, movement, or thought.

As chairman of the Christopher Reeve Paralysis Foundation, Reeve uses the full force of his celebrity to raise funds for and promote communication about research into a "cure" for spinal cord injury paralysis. (See "Unity of Purpose," page 44.) His foundation has even organized a consortium of leading neurology research labs. (See "Ring of Science," page 48.) Reeve also serves as PE's editorial advisor for "Discovery! Neurology."

During our conversation, Reeve pushes an even broader agenda: getting pharmaceutical companies to realize the huge market potential in spinal-cord research for a host of neurological conditions. He implores companies to put their attention, and their investment, into enterprises that are creating breakthroughs in new technologies promising wide therapeutic application.

We meet Reeve at his large but comfortable country home in Bedford, New York, where a large, friendly labrador lies curled by the fireplace and the cold-weather sun shines brightly through many-paned windows.

Reeve is the ideal patient advocate--a lay expert in the field of neurology and a pragmatist in business concerns. His call for greater industry investment in spinal cord research is "not a plea for charity, but a sound business proposition" because of its relevance to more widespread neurological disorders.

As we enter the study, Reeve has a full set of papers spread out on a tray before him. The extent of his preparation reflects his enthusiasm for our common project.

Reeve: I dictated a lot of notes for the interview, because I wanted to convey specific thoughts. Usually I do it off the top of my head, but I want to be accurate.

PE: Thank you. What are the major things you've learned since your injury that you would like to share with our readers?

Reeve: People need to understand that a cure for spinal cord injury paralysis is not only possible but probable. And now the major question is not just basic science; it's funding, sufficient funding for moving from the rat model and pig model to the human. That's very expensive.

But one of the most conservative members of our consortium, Dr. Martin Schwab of Zurich, recently stated that he foresees a day in the not-too-distant future when, due to novel therapies, spinal cord injury (SCI) patients can expect a much better recovery. More than ten years of research led him to that conclusion, because the basic work was done in the late '80s when he discovered a protein that inhibits the regrowth of nerve fibers in the spinal cord. Schwab has developed antibodies against the nogo protein and has demonstrated regeneration and functional recovery after its use in animal models.

It has since been proven that nerve regeneration is possible, when for centuries it was believed to be impossible. However, because every injury is different, many approaches will be required and there will be no magic bullet.

PE: What is the biggest obstacle to further progress?

Reeve: The scientists are ahead of the funding right now, and that's very unsettling to those of us in wheelchairs, because we don't know whether it will be three years, five years, or 15-20 years before we see treatments. It's going to depend on money. But scientists are beginning to anticipate and plan for translational research, moving from the bench to human applications.

The most important thing that pharmaceutical companies ought to consider, in my opinion, is that research into spinal cord injuries is providing important information to researchers studying other central nervous system disorders like Parkinson's, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). It even extends to diabetes and stroke. So any research on the spinal cord can benefit millions of Americans who are living with those diseases and conditions.

There is a drug called 4-AP currently in multicenter studies that temporarily boosts the ability of nerve cells to send signals up and down the cord when the myelin has been damaged. It is showing real promise and can help both SCI and MS patients.

Stem cells--both adult stem cells and human embryonic stem cells--will play a major role in treating all those conditions. This is another area where the pharmaceutical companies could step in with applications. Stem cells from the umbilical cord are now being used to cure hemophilia. Adult stem cells from bone marrow are being used to fight bone marrow cancer. That is already happening in humans.

PE: You believe pharma companies could do more?

Reeve: What we need is for pharmaceutical companies to take reasonable risks but also to understand that the downside is minimal, because the science has progressed so well and it's quite clear there are millions of people suffering. The government, the pharmaceutical industry, venture capitalists, and foundations must work together to find cures as quickly as possible.

As a spinal cord injury victim, I am glad to say that I am not just speaking for myself when I testify before Congress or speak to the media. There are one-quarter million of us in the States and about 1.5 million people worldwide with spinal cord injuries, and approximately 100,000 new injuries will occur worldwide each year.

But I am speaking on behalf of the research that will help cure many other conditions of the brain and central nervous system, which really affects all families. I know that it is difficult, particularly for politicians and for pharmaceutical companies, to work on orphan drugs or to see the potential in what seems to be a small marketplace. But my point is that all those conditions actually represent a huge marketplace now.

PE: Do you have an idea of the scale of funding that the pharmaceutical industry would need to move the new treatments forward at top speed?

Reeve: In the mid-1990s, a number of researchers quoted a figure of about $300 million needed to develop treatments and cures for spinal cord injury--before the discovery of what stem cells can do. Stem cells would do much more than make spinal cord injuries go away; they would have a huge crossover impact. And $300 million is really not a lot of money.

In human trials, funding for the first phase of safety studies on a group of 8-10 patients is not difficult to find. A second-phase trial might take 20-30 patients and cost about $10-$12 million. Again, that money is not so hard to come by. But the third phase might require a base of 500-600 patients. I certainly hope that the Phase I and Phase II trials will be conclusive and successful, and therefore the job of raising the much larger amount will be easier--particularly when they demonstrate multiple applications of the tested entity.

PE: Do you think the industry also needs to invest a lot more at the basic research level--in the kinds of labs your consortium includes and perhaps others as well?

Reeve: The spinal cord is a complex part of the body, and it is very difficult to work with, so the basic science still needs support. Only when scientists completely understand the biology of both the intact and the injured spinal cord on the molecular and systemic level can they come up with rational interventions.

Some researchers are focusing on basic science, while others are moving into human trials right now. Sygen (GM-1 ganglioside) is currently in a US Phase III clinical trial as a chronic injury intervention. There is also a multicenter-supported ambulation trial underway in this country and in Canada using weight-supported locomotor training on a treadmill. More and more and more centers throughout the world are beginning to use that therapy.

PE: ...to keep the body in good shape?

Reeve: No, actually to do much more than that. Scientists at UCLA began using that approach with SCI subjects about eight years ago. There are clinics and laboratories in Canada, Germany, and Switzerland that continue to evaluate the effectiveness of this intervention. After only 60 days of walking on a treadmill for about an hour a day, some severely injured spinal cord patients have been able to walk across the floor on their own, generally just using a cane. They're not cured in the sense that the spinal cord functions normally, but their spinal cord has learned to step in a new way, and the memory of that stepping is stored in the spinal cord.

The first time I tried locomotor training on a treadmill, although of course I have to be supported by a harness, I was able to step normally just by the trainers appropriately assisting movement of the limbs and shifting weight, causing the spinal cord to respond and and pick up a regular gait. The treadmill is the kind you find at any gym, but there are millions of people in wheelchairs right now with injuries in the T levels who could get out of those wheelchairs and no longer be a burden to their insurance companies. Our foundation would like to see treadmill-walking therapy introduced in rehab centers all over the country.

Innovative Support

Not waiting for industry to fund basic research on the spinal cord, Reeve has worked successfully to convince state legislatures to create research trust funds that support and coordinate the work of many spinal scientists. Logically, the programs draw their financing from the source of most spinal injuries--reckless drivers.

PE: Your organization has taken many different approaches to research funding, including the idea of state-established trusts funded by surcharges on traffic fines. Do you see that model spreading state by state?

Reeve: It has already spread. In New York, the surcharge on moving violations raised millions for research in just the past year and a half. But most important, the board of the NY Spinal Cord Injury Research Trust is promoting partnerships with scientists from other states, because no single laboratory can accomplish the job alone. It is an exciting development for scientists in New York to be reaching out to scientists in other states. They're partnering on experiments.

I believe ten or more states now raise funds from surcharges, and all of them have agreed to such partnerships, looking for the biggest bang for the buck. And that will help shorten the timeline.

PE: It seems easier to accomplish that in a bipartisan way at the state level than it would at the national level.

Reeve: The problem at the national level is getting past all the groups that want a piece of the pie. When I was working on pushing this program through in New York, I made the argument to Governor Pataki that 49 percent of all spinal-cord-injured people are hurt in a car accident. And we have to remember that the people in those cars do not represent any special interest group. I believe that made the difference.

Sometimes, special interest groups that ask for a check-off on a ballot or a surcharge are rejected by the legislature for being too narrow in their application. But we had two factors in our favor: one, the statistics on who's injured--that it could be anybody riding in a car; and two, that the money raised will not only accelerate spinal cord research but also help bring treatments and cures for the other diseases of the brain and central nervous system.

PE: New Jersey and California are home to many important companies in this field. Is there an opportunity for them to participate in the state programs?

Reeve: Yes, of course. The way it works is that the money raised goes to scientists who apply for grants, and they generally are from the university system. This is the seed money that will get us to human trials more quickly, particularly to Phase I and Phase II. Then we may use Phase I and Phase II to convince a pharmaceutical company to come in for Phase III, to demonstrate the worthiness of their investment and minimize the risk.

It would be great if we just had an open checkbook. But, of course, every company needs to look at its responsibility to stockholders and the profit margin. That is perfectly understandable. My hope is that when there is convincing data that a treatment is safe for Parkinson's, ALS, or spinal cord injury, the pharmaceutical companies will step up to the plate.

I know that many of these companies have large research and development budgets. This year alone, Bristol-Myers Squibb will spend about $4.7 billion on research. So no one is accusing the pharmaceutical companies of not doing research. It's just that there is an information gap.

The role of a foundation like ours can be to help bring it all together so we could go to a major pharmaceutical company with convincing evidence that spinal cord injury research is not an isolated field, so they should participate. I believe we are looking for a win-win situation.

PE: How far could the new breakthroughs extend?

Reeve: They would extend to millions of people, including those who are working at the pharmaceutical companies and their families. This subject really is relevant to the public, the insurance companies, and the pharmaceutical companies, because we all have families and we all have the same vulnerability to chronic and catastrophic illness or disability. In a heartbeat, any executive at an insurance or pharmaceutical company could go from being a healthy chairman of the board to an intensive care patient for a spinal cord injury--which would be a life-changing experience.

Where From Here?

Reeve challenges pharmaceutical companies to unleash their creativity in a commitment to curing spinal cord injuries and related disorders.

PE: After talking about this issue for several years, do you sense that any pharmaceutical companies are ready to do anything?

Reeve: Yes. There are several companies now, just in the field of spinal cord injury and its crossover applications, that are working with scientists and funding their research as they move from basic science to clinical applications. Novartis is working closely with Dr. Martin Schwab on antibodies. Geron is working with Dr. John McDonald at Washington University on remyelination. And a recent study at Yale, taking the olfactory gland from a pig and transplanting it into the spinal cord of a rat, thus achieving regeneration, was funded by Alexion.

PE: Aside from all the wider applications, what a tremendous psychological boost curing spinal cord injuries would be to the industry!

Reeve: Of course. Even simply in terms of public relations.

PE: Working on what amounts to a miracle.

Reeve: The opportunities are there. No one is asking pharmaceutical companies to take unreasonable risks or to go out on a limb and jeopardize their business. But the point is that research has progressed so much that pharmaceutical companies won't have to go far out on a limb--just a little way--and the branch won't break.

PE: Sometimes it just takes a little extra courage. When Dr. Paul Janssen introduced antifungals and antiparasiticals back in the early 1960s, he was told that there was no market for the third-world drugs he had developed in the old Belgian Congo. He said that he was going to make a market. Those inventions turned out to have a huge application, not only for humans but for animals, even in crops and plants, using the same chemicals.

Reeve: Think about aspirin, which originally was developed as a mild cure for headaches and muscle pain. I don't think anyone who worked on developing aspirin could have foreseen the day when doctors would routinely prescribe it as a blood thinner. But that won't happen if the pharmaceutical companies don't step up to the plate now. In doing so, they would make all kinds of ancillary discoveries and reap the benefits.

Integrated Opportunities

With pharmaceutical treatments, creative thinking must include calculating the right business and marketing equations for a cocktail of interventions involving stem cells, growth factors, gene therapy, and receptor-based biochemistry. But Reeve emphasizes the value of those platforms as proving grounds for wider applications.

PE: Can you envision how those new treatments might enter into routine use and what they would mean in a patient setting, including your own? It will probably be more than just popping a pill. In the pharmaceutical business, you have to think about how to integrate several different approaches at the same time.

Reeve: Integrating approaches is the source of opportunity for the pharmaceutical companies, because no two injuries are the same. So, repair will depend on a host of factors, including the type of injury, the level of injury in the spinal cord, and whether the injury is acute, subacute, or chronic.

Opportunities exist to minimize the damage right at the time of injury and up to a few hours afterward. Some scientists are working on this. Others are researching how to prevent ongoing cell death in which cells in the cord continue to die for six months after the initial trauma.

Some scientists are working on pain management; others are working on regeneration, which will be needed in cases of chronic injury. Regenerating axons will need to be guided to their appropriate targets on the other side of the spinal cord lesion. Other researchers are working on remyelination, which is like putting the rubber coating back on a wire so that it will conduct an electrical signal efficiently and effectively.

In the end, dozens of different drugs might be involved just to treat the spinal cord. That does not include what they might do for other diseases.

PE: How about repairing nerve damage from surgical wounds? Millions of people, following operations on all parts of the body, suffer neurological damage.

Reeve: Also in brain injury and stroke--the principle of regeneration applies there as well. If I were the CEO of a pharmaceutical company, I would tell my employees, "We have to think outside the box." Because all bets are off and conventional wisdom is being discredited almost every day.

PE: Do you have an example?

Reeve: In this country, we are able to meet crises head on simply by using our intelligence and resources. There's one example to which I refer all the time,--the Apollo 13 mission to the moon. As the crew was on their way back to earth, CO2 levels in the cabin were building to a very dangerous level. It finally got to the point where the astronauts only had 30 minutes to live. Engineers on the ground had nothing on their checklist that covered that problem--nothing in the manuals. So they brought out cardboard boxes, duct tape, and other improvised materials, communicated the instructions to the astronauts and saved their lives.

That is an example of American excellence in coping with an emergency. If we were to think of the suffering of the millions of people who have Alzheimer's, Parkinson's, MS, or spinal cord injuries as an emergency of the same magnitude, the whole landscape would change.

Sometimes researchers become obsessed with doing an elegant study that does not really address the needs of a human being. I often urge them on their way home at night to go by the rehab center at a nearby university and spend ten minutes watching fellow human beings struggling to move a finger or to take one step forward. If they were to do this, I think that their sense of urgency would intensify.

PE: If you haven't experienced or you haven't seen it...

Reeve: Yes. If scientists or clinicians put themselves in the other person's shoes for a while, it would have a profound effect on the entire industry. One of the men I admire most in the pharmaceutical industry is Robert Wood Johnson of Johnson & Johnson, because in his immediate family, there are both diabetes and lupus. He understands first hand what that means. And he is using his own money and the resources of his company to do something about it.

Market Access

Despite the huge sales potential of treatments for neurological disorders, companies and patients in the future will face some of the same opposition they face today--mostly from reluctant reimbursers, private and public. Not even someone of Reeve's economic status is immune.

PE: You mention in your book, Still Me, that the patients most likely to benefit from a cure are those whose bodies remain in the best shape. But many people see their bodies deteriorate over time because they don't have much support from insurance or Medicare for the necessary treatment and physical therapy. We tend to think of movie stars as not having to worry about finances, and yet it is clear that you also struggle with insurance and the cost of care.

Reeve: The insurance industry is still governed by outdated risk management systems. That prevents them from funding proactive approaches such as treadmill-walking therapy. Yet there has been a high rate of success with that therapy in patients who have some remaining muscle function below their otherwise severe injury.

That therapy alone can get some people out of wheelchairs, back into the workforce, where they would no longer be a burden to their insurance companies. Yet the only patients who can obtain it are those lucky enough to be chosen for a study at one of the centers. So only a few hundred people have benefitted, whereas that number could be in the tens of thousands.

I believe it is time to put an end to the built-in adversarial relationship between patients and insurance companies. Right now, insurance companies continue to deny treatment any reasonable person would consider essential; for example, in my case, a backup ventilator. I am ventilator-dependent 24 hours a day, and if this ventilator failed--and all machines do fail at some point--it would be very dangerous not to have a backup. Yet when I applied for a backup ventilator, I was denied, not just once but several times.

Only about 30 percent of patients who are denied such care or equipment fight back and even go so far as to threaten lawsuits. Finally, they may get what they need. But 70 percent roll over, and that, of course, is cost effective for the insurance companies. My point is how much more cost-effective it would be if insurance companies paid for reasonable, proactive therapy.

I believe that in the 21st century we face a challenge that can be overcome through education. That challenge is to convince major corporations that ethical free enterprise will be to their greatest advantage.

No Time To Waste

On a personal as well as a universal level, Reeve makes a strong case for urgency in supporting research for SCI and other neurological disorders. (See "Stem Cell Debate," page 40, and Political Savvy," page 50)

PE: How much difference can the pharmaceutical industry make at this time?

Reeve: There has never been more confidence that the damaged spinal cord can be repaired. The discoveries being made in the laboratories with animal models are absolutely extraordinary. Of course, the greatest obstacle is sufficient funding to support further research. Moving from the lab to clinical trials requires money--lots and lots of money.

I have said this before, but I will say it again. Every morning I wake up and worry about the timeline. I feel like a prisoner not knowing if he will make parole, but trying to be a model prisoner so that the parole board will be lenient. Unfortunately, we really are prisoners of money, or rather the lack of money.

The most urgent task is changing the mindset and to get pharmaceutical companies and insurance companies into the loop, as well as FDA. We must get them to believe that the scientists are really onto something now. For so many years, all these diseases were considered incurable. And it is very difficult to change mindsets. But we cannot just accept the status quo.

We don't accept the status quo at the Christopher Reeve Paralysis Foundation. We try to ensure that scientists with cutting-edge ideas are adequately funded. But no one is asking for charity. This is a reasonable business proposition.

PE: But you also hope to benefit...

Reeve: Of course, I want to get out of the chair. But I am not just speaking for myself. There are millions of people who will live with some kind of neurological disorder. That is why I can go to a pharmaceutical company and to the NIH and say, "Please spend the money." It is not charity. It is not philanthropy. It is a great public service, but it is also ethical free enterprise. That really should be the model for capitalism in the coming century.

RELATED ARTICLE: Stem-Cell Debate

Most research on stem cells--including how to differentiate the cells into nerve tissues--has employed human embryonic cell cultures. That has also engendered all the usual controversy over any science that involves the "unborn." Scientists harvest the cells from eggs left over from in vitro fertilization, after selection and implantation of eggs in the womb. It is a plentiful source, with hundreds of fertility clinics providing surplus cells. More recent research may moot the controversy with the use of adult stem cells, which would be harvested from the patient's own body. Despite that breakthrough, Christopher Reeve has continued to lobby Congress and the National Institutes of Health (NIH), with success, for federal funding of stem cell research. He explains why:

"Human embryonic stem cells have the greatest potential because they are completely undifferentiated. Research is being done to take adult stem cells from the bone marrow and turn them into neurons. However, it required a more complicated process and was much more difficult to do than working with human embryonic stem cells.

"There are several points I wish people would understand about human embryonic stem cells. For the last 40 years, there have been fertility clinics. A woman who participates in in vitro fertilization has always had three choices regarding what she can do with the unused embryos: one is to discard them, two is to freeze them for the future, and three is to give them to medical research. I am unaware of any legislation introduced to shut down those clinics or to regulate this practice. I am also not aware of any significant protest other than an outright ban by the Catholic Church.

"Now that scientists have discovered the virtually unlimited potential of human embryonic stem cells to cure disease, I don't understand why there is a backlash against the use of these cells. Again, I think it simply comes down to understanding. I recently spoke before a group of House staffers about this issue. I tried to explain the difference between a discarded embryo that will never become a human being and an embryo that has been implanted in the womb and will become a fetus. Scientists are not asking for those fetuses. They are not asking women to have abortions so that they can use those fetuses for research, even though research on fetuses is legal in this country. It is all backwards.

"Fortunately, the recently drafted NIH guidelines were endorsed by President Clinton and federal money now is being spent on disseminating human embryonic stem cells. It is my hope that any politician, from the new president on down, would be willing to listen to the experts and to understand that this is not abortion and that scientists are not advocating abortion.

"Another important factor is that harvesting human embryonic stem cells is not an open-ended project. Within two years enough embryonic stem cells could be harvested to suit the needs of scientists for the near future. There are, in fact, more than 100,000 frozen embryos, some of which could be used under these guidelines. Therefore, this research is so critical. Without it, we will not achieve scientists' very practical goals, and it would be a tragedy if a major initiative was launched against the use of these cells.

"There are two important objectives: one is to convince politicians and the public that embryonic stem cell research is critical; the other is to convince the pharmaceutical companies of the astounding opportunities that lie ahead for them. If we can accomplish those two objectives, we would begin to see cures very soon. We would be talking about 3-5 years instead of 15-20 years."

RELATED ARTICLE: Unity of Purpose

In 1999, the Christopher Reeve Foundation merged with the American Paralysis Foundation to form the Christopher Reeve Paralysis Foundation. Reeve serves as the highly active chairman and chief promoter of the organization, which has made its mark with a combination of grass roots and celebrity fundraising, coupled with smart grant giving for spinal cord injury research and care and coping issues. Here, he discusses the foundation's support, purpose, and initiatives, including a research consortium, young scientist awards, and "quality of life" grants to local care groups. Reeve talks about the contribution sources, grant recipients, and the future of the consortium.

Money Coming In

"Contributions come from a lot of different sources: from direct mail, from individuals who have a family member who has been injured. They come from smaller foundations that funnel their local fund raising to us, such as the Emily Hunt Foundation in Indianapolis, the Alan T. Brown to Cure Paralysis Foundation, and several others around the country. Fortunately, we now have gained real credibility and greater resources. So rather than a lot of little groups trying to be heard, we do our best to represent them.

"Corporate donations have come from many sources, but especially the healthcare industry and, in particular, from a company called Health Extras. Much of our revenue comes from private donors and from a major fund raiser we hold every year in New York called "A Magical Evening." Last year we raised $2.4 million in one evening.

"We have affiliations with other organizations such as the New York Rangers. Every time the Rangers score on a power play, that represents $500 for our foundation. We also do something called Super Skate every year where we bring celebrities to play with the Rangers in Madison Square Garden. They perform a skills competition, and that event brought in quite a lot of money last year. We did not quite sell out the Garden, but almost.

We also have a golf tournament led by Karrie Webb, the number-one female golfer in the world. People donate money to play and to receive coaching from her. Every March, in partnership with the Vail Valley Foundation, we have a fundraiser in Vail, Colorado. Again, we bring in corporate leaders who enjoy racing with professionals and celebrities--we mix them all together. There is also an auction that helps us to raise money. There are four or five main avenues of fund raising."

Money Going Out

"Every year there are approximately 500 research and Quality of Life grant applications and we generally narrow it down to about 35-40 new research awards and 10 Quality of Life grants. Last year we awarded more than $4 million in research grants. In the past, we were only able to provide modest grants of seed money ($25,000-$30,000). Now we give individual awards of $100,000 per year.

Working Together

"We have a consortium of eight of the world's top researchers. To have those eight working together is our most important achievement, because scientists are used to working alone. And each has his own methodology. Now they realize that it is essential to work together and they are really enjoying the collaboration."

"If we are asking scientists to work together, then our private foundations should work together as well. Michael J. Fox and I have talked several times. We both advocate stem cell research for both conditions [spinal cord injury and Parkinson's disease, which Fox has]. We both have testified several times and have written articles for magazines. I wrote an article for Time awhile ago, and he wrote an op-ed piece for the New York Times.

RELATED ARTICLE: The Invisible Menace

Consider this scenario--you are going about your normal daily routine when, without warning, your autonomic nervous system, which controls involuntary functions, suddenly begins to misfire

Blood pressure rises, sometimes to stroke levels. Heart rate and breathing patterns are disrupted. Muscle spasms, skin crepitation, and profuse sweating engulf your body and mental concentration becomes difficult.

That uncontrollable physical reaction is autonomic dysreflexia (AD), a condition long associated with higher-level (T-10 and above) spinal cord injuries. It is now appearing not only among spinal cord injury survivors but in the increasingly larger population of those who have had upper-level spinal surgery, such as disk repair, and those whose surgeries have affected major peripheral nerve systems.

In spite of AD having a long, well-documented history, traditional treatment remains rudimentary--consisting of Valium (diazepam) and antispasmodic drugs such as Baclofen (liorisal) and Dantrium (dantrene). In addition to a host of side affects ranging from addiction to psychosis to permanent liver damage, those interventions have a low level of effectiveness, leaving the field open to new pharmaceutical approaches. Recently, blood-pressure-regulating drugs such as Inderal have shown results in acute use, but they generally require professional administration and are unsuitable for chronic, preventive use at the levels required for relief.

Caused by noxious stimuli such as pain, AD is a massive response by the autonomic system to the stimulation of the central and peripheral nerves. That response can often be mitigated by removal of the stimulus, but often palliative, symptomatic relief is necessary. Current interventions in research range widely, from vascular control to inhibiting the growth of certain nerve structures to cannabinoids.

All of those approaches have advantages and drawbacks--dual activity, unforeseen side effects, and government policy among them. But one of those routes, or a combination, may well lead to an effective, accepted regimen for this dangerous, disabling condition that affects an increasingly larger segment of the population.

--Scott Darroch

RELATED ARTICLE: Ring of Science

Recognizing the need for greater understanding of all aspects of spinal cord injury and therapeutic intervention, Reeve helped establish Christopher Reeve Paralysis Foundation's Research Consortium on Spinal Cord Injury in 1995.

A collaborative network of major laboratories, the consortium includes eight principal investigators and a junior associate from each lab, as well as an independent consortium advisory panel whose members provide counsel to CRPF's director of research and board of directors.

The consortium's goals are far-reaching: to learn more about injury processes in the spinal cord; to target key points in the course of injury for specific therapies; to develop acute intervention strategies to limit degeneration; and to create constructive techniques to promote rebuilding and, ultimately, the reconnection of the injured cord. Moreover, the research agenda pushes for a deeper understanding of the time course of the molecular and cellular activities underlying both degenerative and regenerative events--providing a solid baseline of knowledge about the "windows of opportunity" for selective interventions.

The consortium's eight separate labs, internationally recognized for cutting-edge research in their respective fields, were chosen by CRPF's directors and advisory panel. Although each lab functions independently, the principal investigators meet several times a year for an intensive brainstorming session.

The eight labs are:

* The Black Lab, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway; headed by Dr. Ira Black, professor and chairman, Department of Neuroscience and Cell Biology.

* The Bunge Lab, the Miami Project to Cure Paralysis, University of Miami School of Medicine; team leader Dr. Mary Bunge, professor of cell biology and anatomy.

* The Choi Lab, Washington University School of Medicine, Saint Louis, Missouri; key researcher Dr. Dennis Choi, head of the department of neurology.

* The Cotman Lab, Institute for Brain Aging, University of California, Irvine; headed by Dr. Carl Cotman, director of the Institute and a professor of neurology.

* The Gage Lab, The Salk Institute, La Jolla, California; headed by Dr. Fred Gage, professor in the Laboratory of Genetics.

* The Mendell Lab, State University of New York, Stony Brook; team leader Dr. Lorne Mendell, head of the department of neurobiology and behavior.

* The Parada Lab, University of Texas Southwestern Medical Center, Dallas; lead scientist Dr. Luis Parada, professor of cell biology and director of the Center for Developmental Biology.

* The Schwab Lab, Brain Research Institute, University of Zurich, Switzerland; key researcher Dr. Martin Schwab, head of the neuromorphology department.

--Susan Fenton, Associate Editor

RELATED ARTICLE: Political Savvy

Since the accident that paralyzed his body, Christopher Reeve has been nothing but active on the political front--returning to Congress several times to lobby his cause and to win converts in state legislatures throughout the country. After securing good connections with the Clinton administration, we asked Reeve if it was daunting to face the prospect of a new president. Here's what he had to say:

"One positive possibility is that because there is no mandate, and because millions of people in both parties still think the results are unfair, both sides will have to offer an olive branch. We may actually get more compromise and cooperation in the Senate and in the House than we have previously. Fortunately, more and more politicians are issue-driven rather than driven by tough party politics. For example, Senator Jeffords from Vermont is a Republican, but he sounds more like a good Democrat on many issues than a lot of supposed Democrats.

I hope we are going to have a few years of reasonable cooperation, because basically nobody won the election, even though Bush is going to the White House. So it actually may work to everyone's advantage. Nobody can take the moral high ground.

It is such a relief to know I can go to Congress or to venture capital groups and talk about spinal cord injuries. It was not until about 1998 that the full potential of stem cells was realized. They always knew it existed, but no one really understood the width and breadth of the application. That has changed everything. I do believe that, with patience and without attacking any doubters, we can convince reasonable people in industry and in government that nothing should stand in the way of this research.

There is the possibility of a cure in a few years if they would get involved in pushing for the research. We can't leave our scientists high and dry. Their knowledge base is huge now. The human genome has been mapped. And now scientists are beginning to identify all the genes that relate to neurological diseases and disorders. They know exactly what each of these genes does.

But the problem is, in a changing society, politics and the law are the last to change. We have to turn that around."