Recent advancements in spinal-cord injury research have made big news headlines, but are the outcomes of these studies overhyped?
In April of 2014, Rob Summers shocked the nation when he moved his big toe on his own.
Paralyzed below the neck, Summers began therapy with Susan Harkema, PhD, in a study at the University of Louisville and funded in part by the Christopher and Dana Reeve Foundation and the National Institutes of Health to see if electrical stimulation applied to the spinal cord would help return voluntary movement to paralyzed limbs. It did, and the media ate it up.
Six months later, Darek Fidyka experienced something similar in a study led by professor Geoffrey Raisman, Chair of Neural Regeneration at the University College London Institute of Neurology.
Paralyzed from the chest down, Fidyka underwent a surgery in Poland that transplanted his own olfactory ensheathing cells (OECs) — special cells that form part of the sense of smell — into his spinal cord. The hope was that because OECs can repair the olfactory system, maybe they could repair the spinal cord, too. It worked and, again, the media loved it.
When study results such as these become public, it’s easy to jump straight to thinking “cure,” but Stephen G. Waxman, MD, PhD, director of the Center for Neuroscience and Regeneration Research, a collaboration of the Paralyzed Veterans of America with Yale
University, points out that while hopeful, studies like these require additional time and research.
“ Whether there is a cure around the corner, in that regard, there is still a lot of work to do, and it will take some time to travel the path from hope to a cure,” Waxman says. “But when we discuss from hope to cure we should no longer be asking, ‘Will we get there?’ The question is, ‘How long will it take?’ ”
While Waxman says “the glass is half full, not half empty,” with results like these, there are questions to be asked and things to look for in each study to let you know what it really means for the future of spinal-cord injury before you yell “cure.”
How Many People?
Four people successfully received spinal stimulation in Harkema’s study while just one patient successfully received OEC cells in Raisman’s study.
Left to right: Andrew Meas, Dustin Shillcox, Kent Stephenson and Rob Summers were the first participants in a study to see if electrical stimulation in people with spinal-cord injury could return voluntary movement to paralyzed limbs.
The paper publishing the results of Harkema’s study states the transplantation results were “very encouraging but [have] to be confirmed in a larger group of patients sustaining similar types of SCI (spinal-cord injury).”
That statement alone points out that while the results are promising, it doesn’t mean a cure is around the corner. It’s important to keep in mind that just because it worked this time doesn’t mean it will work every time, especially in Raisman’s case, where just one patient was tested.
Raisman says the results of his study aren’t a cure, but they’ll be continuing on with two to three more patients in hopes for the same results. More testing will have to be done, and Waxman says the tests also need to be done differently.
“Ideally, some of the future studies will be blinded and controlled to rule out the unlikely possibility that the recovery was a spontaneous event (as has occasionally been observed in patients who have not been treated by this procedure),” Waxman says.
What Type of Injury?
Raisman’s study looks specifically at people with completely severed spinal cords at the thoracic level for two reasons: (1) With an injury at this level, you can’t cause any further significant damage and (2) patients with complete transection of the spinal cord have no physical continuity between the two halves of the spinal cord, meaning it has no chance of reconnection on its own.
However, this injury isn’t very common. Most commonly the spinal cord is crushed, rather than completely severed and Raisman admits he and his team aren’t sure their method would work on such injuries.
The method is testing a hypothesis Raisman calls, “The Pathway Hypothesis.” He compares the spinal cord to a freeway where, in the case of spinal-cord injury, it’s as if a roadway was washed away.
“There’s no point doing anything to the cars; you have to repair the roadway,” he says.
Which is what he did with the OECs in the first patient. The nerve fibers of the spinal cord grew back with the help of the OECs and now Fidyka can briefly walk with a walker, drive and bike.
What’s the Purpose?
Waxman says each study will require future studies to address questions that arise. For both Harkema’s and Raisman’s studies, the purpose wasn’t to find a cure per se, but rather to establish a principle that electrical stimulation could help regain function and spinal cord nerve fibers could regrow.
“Both of these papers are based on careful observation. What they have in common is that each paper examined a new potential treatment strategy, and each showed, for a small number of human subjects … some degree of return of function after a severe SCI, more recovery than has previously been observed in humans,” Waxman says. “There were many reasons to expect, from prior research in animal models, that recovery of function after SCI/D (spinal-cord injury and disease) is an achievable goal. These papers, by strong scientific teams, provide proof-of-principle, in human subjects, that a palpable degree of restoration of function is achievable. These are important observations and, indeed, they should give hope to people with SCI/D everywhere.”
Raisman says even if the next two to three patients being tested in this study have successful results, there’s still a lot to be done because all they’ve done is established the principle that the spinal cord can be repaired.
“If we can repeat it I think we will have established a principle that has not been established before, which is that you can reconnect the spinal cord,” Waxman says.
In layman’s terms, Raisman compares “establishing a principle” such as what was done in this study and Harkema’s study to what the Wright Brothers did when they flew the first airplane.
“The Wright Brothers in 1903 flew a plane 100 meters and it was in the air 12 seconds. No use to anyone, but they established the principle that man can fly,” Raisman says. “It took a long, long time to get the technology to get from there to a Boeing jetliner and it will take exactly the same with spinal-cord [injury].”
How Much Longer?
Most studies raise more questions rather than answering, “Is this the cure to SCI?”
In Harkema’s study, questions such as can this help with involuntary functions (bladder, bowel, sexual) and how can we make electrical stimulation more effective arose and further research is being done. In Raisman’s case, questions such as can we do this again, can this be done in other types of SCIs and what are the best cells to use popped up and are being looked into.
“I don’t think that what we are doing now will be what people are doing in the future. What we’re doing now simply showed, like the Wright Brothers, that this machine can fly,” Raisman says. “It’s not going to take any passengers yet, it’s not going to go the transatlantic route. It’s just, it can fly and before that it didn’t.”
So to answer Waxman’s original question, how long will it take?
Waxman says, “We are, in my view, at the beginning of a dawn of exciting progress. There is no guarantee of a cure at today’s dusk, because research takes time. In this regard, hope may not turn immediately into cure. But, as the clock ticks, we are getting closer and closer to the day when, at dusk, we will enter a new age of functional restoration for SCI/D. Most spinal cord researchers would agree that we can’t say how long it will take, and it is impossible to predict which, of the many approaches being investigated, will become a clinical reality first. But it’s very likely that we will get there.”
When looking at results from promising spinal-cord injury research, it’s important to keep in mind that just because a study provides hope, doesn’t mean a cure is necessarily “right around the corner.”
Stephen G. Waxman, MD, PhD, director of the Center for Neuroscience and Regeneration Research, a collaboration of the Paralyzed Veterans of America with Yale University, points out that we should no longer be asking, ‘Will we get there?’ but rather, ‘How long will it take?’
There are a few key words to look for when reviewing a study that can help answer that question. Which “phase” a clinical trial is in helps determine how much more work needs to be done on that particular study.
-Phase I: A trial on a small group of people for the first time to test safety, safe dosage and side effects.
-Phase II: A trial on a larger group of people to determine effectiveness and further test safety.
-Phase III: A trial on a large group of people to confirm effectiveness, monitor side effects, compare it to other treatment and collect data on safety.
-Phase IV: Trials done after marketing to collect data on effectiveness in various populations and long-term side effects.