Life on Wheels (79 page)

Researchers were surprised to observe the reduced pain and spasticity. If anything, they were concerned that pain and spasticity would increase, since 4-AP amplifies nerve signals. All responses were temporary, yet scientists also found that benefits sometimes lasted for as long as four days, even though the drug was no longer present in the blood. Further research is exploring how it is that 4-AP continues to operate in the system.

4-AP works by increasing the excitability of axons, allowing them to better pass on the voltage of a nerve impulse. It also increases the amount of neurotransmitter at the synapse of the neuron, helping the impulse to transmit itself better across the nervous system.

The search continues for a therapy that will permanently restore myelin, either by stimulating the body to remyelinate its own axons or by implanting new cells that would take hold and reproduce. That discovery would cancel the need for the effects offered by 4-AP. In the meantime, human clinical trials of 4-AP are underway at the time of this writing.

Since there is some progress in the use of transplanted cells to remyelinate axons, physicians need to know whether there are intact axons present that would respond to such treatment. Toward this end, 4-AP could serve a diagnostic role because, if someone responds to the drug, it means there are intact but demyelinated axons present.

There is no question that recovery from an SCI will involve many different factors, as described by, Marco Saroni, a research fundraiser with quadriplegia:

Acorda Therapeutics, the first commercial venture established specifically to develop a spinal cord therapy, was established in 1995 by Dr. Ron Cohen. After working at another biotechnology firm, Cohen took a sabbatical to investigate what area of the industry would be exciting and had business potential. He found about 20 different fundraising entities for spinal cord research that were spreading their money around to various universities and research labs, with no coordination of the effort.

The academic laboratories are designed to make discoveries, not to develop them into something useful. A commercial entity is needed to conduct more extensive animal studies, conduct toxicity studies to make sure the therapy is not harmful, and then figure out how to make a pure medicinal grade product. Only then can you proceed with human trials.

At that time, no major pharmaceutical companies were showing interest in spinal cord therapy. They considered the market too small and were not convinced that the research would be fruitful. Another factor in deciding to pursue spinal cord research was the superb animal models developed by Wise Young and his team. Acorda’s capacity to test as many as 3,000 animals per year owes its thanks in part to Wise Young’s animal model.

Cohen gathered together the key players to discuss the issue and found them frustrated with the lack of organization and cooperation among the various funding groups and research labs. These scientists understood that research is of no value unless there is some way for its findings to be approved by the FDA, manufactured, distributed, and sold. These are tasks that happen in the commercial realm, so the spinal cord research community supported Cohen’s efforts to establish Acorda.

Acorda is privately financed but has also received some institutional support. In 2008 the company became publicly traded. Acorda provides funds to its laboratory contractors and is poised to license therapies from the laboratories as they become available. Licensing will provide royalties to the universities where the labs are located, helping them to continue their work. Meanwhile, Acorda gets the right to produce and market the therapy. The first product Acorda intends to market is the drug 4-AP, which helps existing myelin-compromised axons pass on a nerve impulse. The Canadian Spinal Research Organization gained the patent rights for 4-AP and, in 1995, licensed them to Acorda. What makes the product unique is the “delivery method,” a means of having it enter the bloodstream at a specific pace.

Acorda has reached FDA Phase III testing on 4-AP, including a disappointing result that shifted their protocol away from SCI to multiple sclerosis, in which results in controlled testing phases were more positive. The SCI community will nonetheless have access to the drug once it passes its final FDA testing, as doctors will be free to prescribe it as they see fit.

Spinal cord research has not been the kind of popular cause that attracts large amounts of money. Muscular dystrophy has the emotional image of disabled children, a well-known celebrity in Jerry Lewis, and a huge annual telethon to promote the Muscular Dystrophy Association’s fundraising. AIDS has the fearsome quality of an epidemic and the political and cultural intrigue of our society’s struggle with the acceptance of homosexuals. Cancer and heart disease happen on such a large scale at such extreme cost that large contributions by government and individuals seem modest in comparison.

The government has not been making the optimal investment in SCI research through the National Institutes of Health, instead, placing their emphasis on cancer and AIDS research. Lobbying efforts by the disability community have been focused on matters of employment, transportation, accessibility, and civil rights rather than on spending for cure research. The overall budget for SCI research is very small compared to what is spent on cancer research. When you compare it to the $9.7 billion that SCI is said to cost our economy each year—as estimated by the United States Centers for Disease Control and Prevention—it is mere pocket change.

Spinal cord research is now getting more money but, many would say, far from enough. The task of fundraising remains left to a variety of groups that raise money any which way they can, from individual memberships, corporate donations and endowments, to parties, golf tournaments, and the like.

Since the 1970s, a variety of groups have formed and reformed for the purpose of advancing SCI research. One of the first, begun by the wife of a spinal-injured man, was the Bermuda Conferences on Spinal Cord Injury Research, which has given an award every other year since 1972.

In the late 1970s, the Paralyzed Veterans of America, the Spinal Cord Society, the Paralysis Cure Research—formed by spinal-injured people— and the Help Them Walk Again Foundation were active. The Help Them Walk Again Foundation organized one of the first scientific meetings on SCI in 1979. The Spinal Cord Society funded much early research and earned national attention when its computerized walking demonstrations using functional electrical stimulation (FES) were featured on the television show
60 Minutes.

When Christopher Reeve acquired high-level quadriplegia, requiring full-time ventilation for breathing, he began using his public fame and passionate organizing skills to campaign aggressively for CNS research. He joined forces with the American Paralysis Association, which soon transformed into the Christopher Reeve Foundation with the result of higher levels of fundraising and political advocacy. With Reeve’s early death in 2004—and then, tragically, the loss of his wife Dana to cancer two years later—the Foundation has continued, and in fact grown. Now the Christopher and Dana Reeve Paralysis Foundation—reflecting Dana’s very significant role—funds research, advocates, and provides resources for quality of life through their Paralysis Resource Center.

What was once a shifting mélange of groups has now consolidated into a few key entities that have grown and become more stable. Even more, where once they tended to be isolated and competitive, they are now cooperating and coordinating their efforts. The Reeve Foundation has formed the International Research Consortium on Spinal Cord Injury, the mission of which is “to promote structural repair and functional recovery in the acutely and chronically injured spinal cord.” The consortium includes representatives from The Miami Project to Cure Paralysis, the Salk Institute, the University of Cambridge, and the University of Zurich.

There is a dizzying array of research projects being conducted under the auspices of these groups. Each season the Reeve Foundation, the Miami Project, and others all publish newsletters. The newsletter pages are graced with the faces of scientists next to their microscopes or banks of mysterious electronic devices, with summaries of their projects in very detailed terms. This is not reading for the average nonscientist, but it sure gets across the scale of talent at work. A few random examples:

Dr. Robert H. Brown of Massachusetts General Hospital is working on a “non-viral vector for the targeted delivery of neuroprotective proteins to spinal cord motor neurons.” The intent is to limit cell death from free radicals immediately after injury.

Ron McKay, PhD, of the National Institute of Neurological Disorders and Stroke has been following up on a discovery made in the early 1990s. Stem cells in the brain and spinal cord have a unique ability to multiply and mature, giving added hope to the possibility of transplantation of cells.

Jack Diamond, PhD, of McMaster University in Ontario, Canada, is exploring the “functional consequences of primary afferent intraspinal sprouting.” Injured nerves often send out fresh sprouts that can’t find a useful connection. This research attempts to find a use for the degree of regeneration that already takes place in the injured spinal cord.

L.J. Stensaas of the University of Utah has studied the spinal cord of the newt. He found that astrocytes—cells normally found in nerves that provide nutrients—play a role in removing degenerating nerve axons and then act as a base for growth of new fibers.