W2W Part 3: Stim Up, Stem Down

Posted by Sam Maddox in Research News on November 21, 2016 # Health, Research, Technology

One last blast from Minneapolis and W2W. Spinal cord stimulation got a lot of attention at this year’s symposium, partly because of a clinical trial at Mayo, and partly because the new state SCI funding we mentioned previously is supporting an upcoming stim trial at the University of Minnesota.

Kendall Lee is a neurosurgeon/researcher at the Mayo Clinic near Minneapolis. He makes a good part of his living putting in brain implants to treat people with Parkinson’s and other movement disorders. A few years ago he was chatting with Peter Grahn, a young Ph.D. in neural engineering at Mayo. Grahn’s priorities regarding therapies for spinal cord injury are sharpened by his own paralysis, the result of a 2005 swimming accident. Lee noted that his implants had been working pretty well in the brain. “I wonder if we could use something like this to reanimate paralyzed limbs?” he asked Grahn.

Not long after that, Lee was invited to a dinner where he was seated next to Reggie Edgerton, the UCLA scientist and doyen of spinal cord stimulation. “That was the first time I had heard about epidural stimulation and what was being done by Reggie and Susan Harkema. They were reporting that with stimulation, patients were regaining volitional control of paralyzed limbs.”

Lee recalled that he was dubious. “I’ll be honest,” he said. “Everything I’d been taught said it wouldn’t work.”

But Edgerton, who’s spent 40 years exploring the automaticity of the spinal cord and then trying to tap into it, made quite an impression on Lee. One of the hallmarks of scientific research is replication. If an experiment works in one lab will it work in another? With Edgerton onboard, and money from Mayo, the Believe in Miracles Foundation (Jack Jablonsky family) and the Neilsen Foundation, Lee set up a clinical trial to repeat the exact human experiments that the Harkema group in Louisville had done, the ones for which they were reporting remarkable results in four patients (and of course the work upon which the Reeve Big Idea is based.)

So far, Lee and his team have operated on a single patient, an ASIA A (no motor, no sensory below lesion), T6 from a snowmobile accident. First they trained the young man on a treadmill for almost six months. He was still complete, no change. On to surgery. Lee says he put in a type of electrode that he has implanted many times in patients for pain.

“On the second day after the stim was applied, the patient could move his leg.” Later the patient was able to stand unassisted. Lee was astonished.

“I set out to get to the truth,” Lee said. “Is this for real? If it’s not true I want to prove it’s not true. But I think we have shown that yes, there is tremendous hope for the use of epidural stimulation as an intervention in people with paralysis.”

So, what’s next? The replication study is now enrolling patient number two. And Lee is ready to jam. He said he has formed a team of 50 at Mayo; they’re looking for more money and will begin a trial of ten more patients, hoping to see if the epidural stimulation can positively affect bowel, bladder and sexual function.

Said Lee, “This has been the highlight of my career.”

Next up, David Darrow, an enthusiastic and empathetic young neurosurgeon at the University of Minnesota who said he no longer found it acceptable that he had to tell newly injured trauma patients that there was nothing he could do for them. He had routinely been implanting devices into the brain and thought, also after hearing about Edgerton’s work, that maybe the spinal cord would respond to “really really deep brain stimulation.”

Darrow got $125,000 from the Minnesota SCI/TBI fund to set up a trial to implant epidural stimulators in spinal cord injured patients. He says they’re about ready to start enrolling.

One other note from W2W. Stephen Huhn, another neurosurgeon, presented data from the now-defunct Stem Cells, Inc. clinical trial. As you may recall, this trial dosed 17 patients in Europe and the U.S. with an adult neural stem cell line, derived from fetal tissue . We’ve been covering this from the get-go, partly because it seemed to have upside, and partly because the cells were first tested in animals by Aileen Anderson, at UC Irvine, who is a member of the Reeve International Research Consortium on Spinal Cord Injury.

We reported a year ago how quads who got the stem cells got a little recovery of fine hand function: “Five of six motor complete quads treated long after their injuries with stem cells recovered strength in their hands. Four got better dexterity and fine motor control in their hands and fingers. Three treated patients were able to pick up a key, put it in the lock and turn it 90 degrees.

Here’s Huhn himself, enthusing last November about those results: “These findings,” he said, “demonstrate the ability of our HuCNS-SC® cells to improve both muscle strength and motor function, thereby changing the trajectory of recovery following a spinal cord injury.”

Modest but meaningful recovery? That’s what they were telling us. Indeed, restoration of hand function would be huge to people limited by quadriplegia. But a meaningful patient outcome wasn’t enough -- investors don’t want the trajectory of a bunt single, they want to see doubles off the wall. Or homers out of the park.

Stem Cells, Inc. suddenly pulled the plug on the trial last May. Yes, there had been a pattern of recovery, Huhn told W2W, but not enough to keep burning investor cash -- he said it would have cost another $35 million to complete the trial. He said to not worry, failure is common in brain science trials. Alzheimer’s, for example, has a 99.5 percent failure rate.

“But for us,” said Huhn, “this was not a failure. It was an outcome.”

I disagree. It was a failure. We don’t know if it was a failure of the science; the trial data is not fully available. But this is surely a failure of a corporate clinical trials system that is bred upon short term gains, fed by public relations exaggeration, and tied to the myopia of the small cap stock markets. This system is not capable of encouraging or rewarding incremental success.