A Lot to Be Hopeful For

Dr. Wise Young says SCI therapies abound. Clinical trials are key.

By Rob Ingraham

Recently returned from a year abroad where he helped organize the first, and largest, clinical trial network for spinal cord injury (SCI) therapies in China, Dr. Wise Young gave a ringing endorsement of the burgeoning therapeutic possibilities in development overseas and a plea for getting more clinical trials underway in the United States.

Young, who holds the Richard H. Shindall Chair in Neuroscience in the Department of Cell Biology and Neuroscience at Rutgers University in New Jersey, delivered the Tri-Association Keynote Address at a plenary session of the 2007 NASCICDE conference in Orlando Fla. that drew enthusiastic attendees from American Paraplegic Society, American Association of Spinal Cord Injury Nurses, and American Association of Spinal Cord Injury Psychologists and Social Workers. “This group is where the rubber hits the road in terms of spinal cord injury,” he said. And in terms of new and promising therapies, “There’s a lot going on and there’s a lot to be hopeful for.”

A Challenge from Reeve

Recalling a conversation with Christopher Reeve in 1995, Young said that Reeve asked if there would be a therapy that will restore function. “I answered, ‘Yes.’ And, of course, he answered, ‘How long?’ and I said it will take seven years if we are very lucky and we work very hard and we get all the resources. I think we’ve been terribly unlucky and we have not gotten the resources, although we have worked very hard. Why do I say unlucky? Because 9/11 paralleled, not only this nation, but spinal cord research for the last six years. But in any case, in 1995, I told Christopher that there was hope and it was based on the fact that there would be a lot of acute spinal cord injury therapies.”

One promising surgical therapy that has not reached the US but is growing in other countries is “peripheral nerve bridging,” Young said. “It’s not done in the US,” but it “has made an enormous difference and it’s being practiced routinely overseas. Most American neurosurgeons will not even acknowledge that these procedures are there, or that they work.”

Young described a surgeon at the Royal Orthopedic Hospital in London who treated motorcycle accident victims that had torn peripheral shoulder nerves out of the spinal cord. “He took the end of the peripheral nerve, took a rod and poked a hole into the spinal cord and stuck the nerve back in. He did that on thousands of patients and he reported, in 2001, amazing results. What he showed was that axons from the spinal cord grew into those peripheral nerves and re-enervated muscles in the arms.”

Young stated, “As a scientist, this tells me that if you give an axon in the spinal cord a path to grow, they not only take it, they’ll take it and grow all the way and connect to the end. This is prima facie evidence of regeneration in the human spinal cord. You’ve given them a peripheral neural pathway; they’ve taken it and they’ve gone all the way.”

Recovery of Function

Young reported that physicians in Bonn, Germany, reported that they were able to get 70% of the people who had never walked after SCI to recover walking when they trained them on weight-supported treadmills.

More recently, a UCLA study reported that treadmill ambulation “can restore function to as many as 90% of people with incomplete spinal cord injuries,” Young said. “The surprising part of this study is that they had a control group and 90% of them walked, too… All of a sudden we discover that over 90% of the people can recover walking and one of the frightening possibilities is that the reason why incomplete patients did not walk prior to 1997 was because of the practice by doctors that they shouldn’t even try. This is called a ‘nocebo’ effect, which is the opposite of the placebo effect. The nocebo is the deleterious effect that occurs when a person in a position of authority tells a patient that they are not going to recover, or they are going to do worse.”

Regenerative Therapies Abound

“There are more regenerative therapies than we can throw a stick at today,” Young continued. “There are over 100 therapies today that have been shown to regenerate the spinal cord.” One such therapy, transplanting olfactory ensheathing glial cells, has been undergoing numerous clinical trials is China. “Olfactory nerves regenerate through adult life; they are the only nerves we know of that regenerate continually and it’s been speculated since the early 1990s that the special cell—the olfactory ensheathing glial cell that are born in the nasal mucosa, migrate to the olfactory bulb and enter into the olfactory nerve—that these cells are responsible for the ability of the cells to regenerate and it was proposed in 1993 that indeed if you transplanted olfactory ensheathing glial cells into the spinal cord that you could get regeneration to occur.”

Young said that, when transplanted to the spinal cord, “You find that they survive beautifully.” One Chinese surgeon, he said, has transplanted fetal olfactory ensheathing glial cells in over 700 patients.

“There are fetal stem cells, neonatal stem cells, umbilical blood stem cells, and there are adult stem cells and there is now work being carried out on all these categories.” But Young added, “Unfortunately, in the United States it’s extremely difficult to do large- scale clinical trials and it’s very, very expensive. But there are many companies that are beginning to show interest.”

During his sabbatical in China, Young helped organize the Spinal Cord Injury Clinical Trials Network. This network includes 18 of the leading spinal cord injury centers with the capability of randomizing 6,000 patients per year. He said that there are over 1 million people in China with SCI and as many as 80,000 new cases every year—over half of which are the result of coal mine accidents.

Young noted that the Network in China will be collaborating with the New Jersey Stem Cell Initiative. He explained that, about three years ago, New Jersey started putting $10 million annually into stem cell research. “In December 2006, they passed a law which allocated $270 million of capital investment for stem cell facilities in New Jersey. This includes $150 million to build and equip the Stem Cell Institute in New Brunswick. They will also allocate $50 million for a stem cell research center in Newark; $50 million for a research center in Camden; $10 million for blood collection facilities; and $10 million for the Garden State Cancer Center.” A referendum on the November ballot seeking voter approval for $450 million to support seven to ten years of stem cell research and clinical trials in New Jersey narrowly failed.

Trials Needed

In conclusion, Young stressed the urgent need for clinical trials. “Many therapies show promise for regenerating and remyelinating the spinal cord and several therapies are ready to go to clinical trails… Much work is needed to prepare other therapies for clinical trials and industry sponsorship of spinal cord clinical trials is beginning. Finally, the first successful therapy will transform this field.”

Despite the progress, Young said he still encounters skepticism within the SCI community, but, “If we’re really claiming to be evidence-based, let us get the evidence first before we say no.”

Comparing the recent surge of state funding to a ball game, Young noted, “We’ve been asking for this ball for a long, long time…The ball is heading toward us…and it’s time for us to take a swing. And we need to hit that ball as well as we can and as hard as we can— and, by the way, we will not have many chances. I was talking to Governor Corzine…and I said, ‘Look, next year the people are going to want to know what we’re doing with the money. And then a year after it’ll be, ‘Well, why haven’t you done this or that?’ And the third year they’re going to say, ‘What have you done with our money? You haven’t come up with anything!’

“I think we need to start working right now to pick some low-hanging fruit …We need to start doing the clinical trials now because the road from laboratory to trial is a long, long time. And the public cannot wait. They will not wait. People will understand if the trials don’t work, but what they will not understand is if we don’t even try.”

Rob Ingraham is senior editor.