From: Genetic Engineering News
June 15, 1995
New Biotech Company Dedicates Itself to Spinal Cord Injury Treatment and Repair
By Marjorie Hack

Ron Cohen, M.D., will be the first to tell you that he is no magician. But if things work out as he expects, Christopher Reeve and thousands of other paralyzed patients in the U.S. may one day salute the strength of Dr. Cohen s dream.

He recently formed a new biotechnology company dedicated to improved therapies for spinal cord injuries. Acorda Therapeutics, Inc. is temporarily based in San Diego, CA, but its team of researchers is literally spread all over the world. According t o Dr. Cohen they all believe that scientists now have the tools to begin to help repair disabled central nervous systems (CNS).

While Dr. Cohen promises no miracles, he is hopeful that the new company will come up with a cocktail of compounds that can help mend some of these damaged systems (or at least key parts of them).

With spinal cords severed or disabled by disease, about 250,000 chronically paralyzed patients in the U.S. are nearly helpless, confined to wheelchairs for what usually turns out to be the remainder of their lifetimes.

It s not just the emotional toll thatís so steep; it s the dollar cost as well, notes Dr. Cohen, who is also the president of Acorda Therapeutics. The per-person cost of spinal cord injury (SCI) averages about $2 million for direct healthcare expens es over the course of a lifetime. That s $5 billion annually for SCI patients in the U.S. alone.

Seminal Discoveries

Dr. Cohen says that ten years ago a company like this one would have been little more than a figment of the imagination. There have been some real seminal discoveries about nerve growth in the last 5-10 years that have made this doable, he says.

These coupled with related advances in genetic engineering led him to believe that with outside intervention, the CNS is capable of regenerating sufficiently to significantly improve the quality of life and reduce medical costs for SCI patients.

Like the Cowardly Lion in the Wizard of Oz, I almost wanted researchers to talk me out of this, says Dr. Cohen, who at first seemed to be the only one committed to helping the process along. To him, it didn t seem like lack of know-how was the s tumbling block. Rather, it seemed that the technology at hand was simply not being applied. The area of spinal cord injury was simply a niche nobody seemed to be occupying, he says.

Three to four months of conversation with scientists worldwide confirmed his independent
observation: In the early 90s, neuroscientists turned the corner in this area. I must have spoken with 50 or 60 leading neuroscientists about my idea to start a company that would focus on new, bioengineered therapies for SCI, says Dr. Cohen. Only one was cynical about the project.

He points out that his use of the term bioengineering refers to the integration of several different technologies and their application in vivo to restore spinal cord function. Genetic engineering and biomaterials development are two of these techniques, he emphasizes.

For example, the company plans to implant cells containing genetically engineered growth factors into injured spinal cord areas. Also, according to Dr. Cohen, researchers have found a class of proteins that promotes the growth of spinal cord axons.

Dr. Cohen, a board-certified internist, is no neophyte when it comes to new corporate ventures. In the late 1980s, he co-founded Advanced Tissue Sciences in New York City. The company focused on developing human tissue constructs for organ transplan ts. The partners worked out of their apartments and used the 23rd street delicatessen as our board room, says Dr. Cohen. Later they joined Art Benvenuto who took over as CEO and moved the company to San Diego in 1989.

Dr. Cohen decided to leave several years ago to start a new venture. Though I was offered a position as chief executive officer at another biotechnology company, I had already become intrigued by the possibility of starting Acorda, he says.

Recruited Scientists

He single-handedly recruited a team of world-class scientists working in the field, including Wise Young, M.D., Ph.D., head of neurosurgical research at New York University and professor of neurosurgery, physiology and biophysics at NYU. Dr. Young has signed on as Acordaís acting chief scientific officer.

We have scientists scattered all over right now in places like California, Switzerland, England, New York, St. Louis, Miami, Cleveland and North Carolina, he points out. As these project teams develop their work and apply it to animal models we w ill start to bring these things in-house. Within a year or so we plan to build our own animal-model laboratory.

Up until now, Dr. Cohen has been paying Acordaís bills himself. Scientists who were brought on board at the entry level have received equity positions in the company. But a few months ago, Dr. Cohen laid the groundwork for a $4 million offering to i ndividuals and venture capitalists. Private donors and paralysis foundations recently provided the first $600,000 in financing.

Start-up costs vary greatly for a company like this, he says. Usually, when new companies go out and raise money and set off on an ambitious R&D program, they reach a high burn rate very quickly. Our challenge was to reduce that burn rate and at the same time get a lot of work done early on, so we chose to go with a virtual company structure that requires little investment in physical plant but big investment in knowledge.

And, according to Dr. Cohen, that knowledge is expanding at lightning speed. Just a decade or so ago, the best in the business believed that, unlike nerves in the peripheral nervous system, those in the CNS would not regenerate if damaged.

This was standard dogma until the 1980s, says Dr. Cohen, when for the first time it was
conclusively demonstrated that given the right conditions, nerves in the spinal cord and brain could grow back. He says that once the evidence was in on that , nerve regeneration became more of an engineering problem.

Molecular Biology

The field has benefited enormously from advances in molecular biology. According to Dr. Cohen, scientists can now study the nervous system at its most basic cell and protein levels. In the last 5-10 years, scientists have discovered all sorts of developmental proteins, cellular adhesion molecules, growth factors and glial cells that actually support growth and play an active role in function, he tells GEN. I believe this will lead eventually to our ability to manipulate and intervene.

Work done by Dr. Martin Schwab in Switzerland in the late 1980s and early 1990s was
instrumental in opening the door to new techniques for regenerating spinal cord tissue. Like others before him, Dr. Schwab recognized that some protein in the myelin in the brain and spinal cord inhibits axons from growing. He developed an antibody that could attach to this inhibitory protein, thus allowing some axons to grow unimpeded, explains Dr. Cohen.

Since then other scientists have discovered additional inhibitory proteins in the brain and spinal cord. Working with these researchers, Acorda will focus on engineering a way of inhibiting these inhibitors, says Dr. Cohen.

He notes that other investigators are taking different approaches. For example, scientists at the University of Florida (Gainesville) are experimenting with the use of fetal neurons to bridge spinal cord gaps. And at the State University of Campinas (Sao Paulo, Brazil), researchers are working on an artificial neural system that shows potential for treating spinal cord injuries.

Phases of Injury

Dr. Cohen points out that when scientists discuss brain trauma, stroke and spinal cord injuries, they are talking about acute, subacute and chronic phases. In the acute phase, clinicians are not so concerned with regeneration, but with preventing nerves from dying in the first place.

Following an injury, certain nerve cells die right away, says Dr. Cohen. But the damage doesnít end there. Left unchecked, bleeding, swelling and inflammation continue and cells die for several days, even weeks.

He is hoping that the work Acorda is doing will help lead to a reduction of those secondary nerve-cell deaths.

In 1990, the National Institutes of Health, working with a consortium of hospitals, conducted a study called MASCIS (Multicenter Animal Spinal Cord Injury Study). It showed that with administration of massive doses of a synthetic steroid (methylpred- nisolone) within eight hours of a spinal cord injury, up to 20% of the function that otherwise would have been lost was prevented. This was remarkable. For the first time, there was a controlled clinical study that showed damage could be prevented, points out Dr. Cohen. Dr. Young was a major contributor to this study.

Regarding the other 20+ neuroscience biotech companies, Dr. Cohen contends that none of them features SCI as their primary area of focus. Most are working on bigger ticket items, like Alzheimer s and Parkinson s disease. In relation to SCI research, he mentions Cephalon (Westchester, PA; CEP-075, preclinical), Regeneron (Tarrytown, NY; BDNF and NT3, preclinical) and Cambridge Neurosciences (Cambridge, MA; glial growth factor II, preclinical).

For now, Acorda is squarely focused on what Dr. Cohen and his colleagues see as a limited number of economically viable, scientifically attainable goals. He believes, however, that there are good odds that Acordaís work will lead to significant improvements in therapies for patients with a host of paralyzing disorders, including multiple sclerosis, brain trauma and stroke.
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