There have been some exciting developments around SCI research in the last few years (see “Stem Cell Trials Show Improved Hand Function, Sensation and Bladder Awareness”), and it’s the China trials that are showing the most progress.
Even so, Dr. Wise Young is far from satisfied.
“We need to bring spinal cord injury back into the mainstream of medicine,” he says. “We’ve been shut out because for the last 12-15 years, there have been no clinical trials of anything. It’s just a bunch of people sticking things into the spinal cord and not doing any control studies, and being criticized.”
For Young, the director of the W.M. Keck Center for Collaborative Neuroscience at Rutgers University, and one of the most visible and educated faces on SCI research, satisfaction and progress are both tied to the same thing: rigorous clinical trials. Young and a huge team of doctors and researchers have been working on just that for the last five years in China, and thanks to some exciting and unexpected results, he is optimistic that the tide may be about to turn.
People are Recovering Function in the China Trials
If you’ve heard Young speak over the last few years, or paid close attention to the releases from the Keck Center or ChinaSCINet — the clinical trial group Young has helped establish in China — you’ve likely heard bits and pieces of the promising findings from his trials there: complete injuries walking again, people regaining bowel and bladder control years after injury. All of the results were published this May in an article in the medical journal Cell Transplant entitled, “Phase I-II Clinical Trial Assessing Safety and Efficacy of Umbilical Cord Blood Mononuclear Cell Transplant Therapy of Chronic Complete Spinal Cord Injury.”
Phase one of the study consisted of eight participants at a site in Hong Kong, while phase two included 20 participants in Kunming, located in China’s southern Yunnan Province. All but one of the participants had ASIA A, or complete, SCI injuries ranging from C3 to T11, and they averaged 14 years post-injury in Hong Kong and seven years post-injury in Kunming. Participants at both sites received injections of umbilical cord blood mononuclear cells (UCBMNC) above and below their injuries, in addition to surgery to de-tether their spinal cords and a large dose of methylprednisolone. The big difference between the two phases was that the Kunming participants also underwent what Young called the “most intensive walking program in the world” — six hours a day, six days a week for three to six months, covering long distances with a rolling walker — while those in Hong Kong did not.
The phase one results showed the processes were safe, and imaging of the spinal cords suggested some regeneration, but no participants recovered motor function. That set the stage for phase two’s surprising results. “We were not expecting very much,” says Young. “However, in Kunming, it rapidly became clear that a majority of the participants were recovering function.”
Young broke down the results in a May letter from the Keck Center:
At one year after treatment, 75 percent (15/20) of the participants in Kunming recovered the ability to walk long distances in a rolling walker with minimal assistance. Thirty-five percent (7/20) could walk without such assistance using either a four-point walker or a crutches. None of the participants could walk more than 10 meters without substantial assistance at the beginning of the trial and a majority were not even able to stand without help. When they went home, some of them did not have devices or people to help them walk and several regressed. However, 35 percent continued to walk and became household walkers, preferring to walk for distances up to 100 meters, but using their wheelchairs for longer distances. Another unexpected finding was that 60 percent of the participants became completely independent including no longer needing any help for bladder and bowel function. In fact, 55 percent stopped using catheters.
“We were quite stunned by these results,” he says. He says he was also intrigued to find that the same participants who had no trouble walking long distances were unable to move their legs if they lay down. “In other words, voluntary movement of the legs is very weak.”
“We believe that what is happening is enough fibers have grown across the injury site to activate the central pattern generator in the lumbosacral spinal cord,” explains Young. “The CPG in the lumbosacral spinal cord contains all the programmed walking motions, and we believe that enough fibers have grown across to activate the CPG so that the person can start and stop the CPG, but not enough fibers have grown across so that they can move their legs at will. They can’t wiggle their toes, they can’t straighten out their legs. But on the other hand, once they start walking, the CPG takes over and they can start and stop and turn — useful walking.”
Young says he thinks the results raise a very important question for future studies to investigate.
“It really opens up the question whether more therapies would work if people actually trained
Young says an ongoing trial in China is looking at whether the UCBMNC are even needed. Participants in that study will receive six months of the intensive walking regimen but no cell transplants.
Similar Trials May Be Launched in the United States
As excited as Young is about the results, he seems even more excited about launching similar trials here in the United States as part of a multi-center, worldwide effort. In addition to China and the U.S., trials would occur in Norway and India. His team met with the FDA in January to review the U.S. proposal and came away with an agreement about how to proceed.
With the money already raised, Young hopes that his team could begin phase two trials in the U.S. by the end of the year. Multi-center phase three trials would be launched around a year later, possibly before the end of 2017.
“So we are estimating that probably the phase three trial will require about 120 patients,” says Young. “We need to do two of them … one, which we want to do with the U.S., Norway, and India, and then a second one that we’ll do all in China. [Another] 120. So it will be a total of 240 participants. And it will be the same one-year long trial. We may find out things from the phase two trial that may change the plan. But we’re hoping that our phase two trials will show that the walking is beneficial.”
One issue Young is working on is shortening the amount of locomotor training required. “6-6-6 is scaring everybody in the U.S.! … To walk somebody six hours a day, six days a week for six months is a multi-million dollar therapy,” he says. “So we are trying to develop ways, including stimulation, [with] which we can shorten this time.” Young didn’t delve into specifics about what types of stimulation his team was looking at, but he expressed admiration and interest in the work of Dr. Susan Harkema and Dr. Reggie Edgerton, leading researchers in epidural stimulation.
Even more than the time demands, the cost of trials could be prohibitive. “The thing that’s holding us back is for every one of these trials, we have to raise the money — it’s not a trivial amount. We have to raise about $60 billion for the trials. And this is not being helped by any company or by the government,” he says. “Right now, all the clinical trials are going on overseas. In the U.S., there’s zero help for the clinical trials to go forward.” Young has made the case for increased funding for SCI research all over America, including the halls of Congress, and hopes a successful U.S. trial will help turn the tide of public opinion.
“We’re going to try our very best to make these trials go ahead and convince people that they’re being done properly,” he says. “We want to make sure we do this right. And as soon as that happens, I’m hoping that there will be many clinical trials. Not just our clinical trials. But there will be maybe half a dozen or a dozen clinical trials going on simultaneously around the world. People will get excited. It’s just like how the first AIDS therapy triggered a dozen other therapies.”