Stem Cell Trials Show Improved Hand Function, Sensation and Bladder Awareness


UPDATE: On May 31, Stem Cells, Inc. announced that it is abruptly ending the Pathway trial, despite the encouraging results below.

I remember talking with Christopher Reeve at his estate in Pound Ridge, New York, in September 2002, a year following the 9/11 disaster that changed the world. He wanted to talk about a different kind of change — his view that a cure for paralysis was imminent and embryonic stem cells would play a central role. He was angry that congressional support was lacking.

Now, finally, human stem cell trials for those of us with SCI and other neurological diseases are in progress and yielding promising results.

Michael-Fraser
“I absolutely see myself improving nonstop.” – Michael Fraser, a C6 quad, one year after receiving neural stem cell injections in the Pathway clinical trials in the U.S.

It took until 2010, six years after Reeve died, for the first human clinical trials involving human embryonic stem cells to get underway in the United States. It never got past the phase one safety arm of the trials. The Geron Corp. ran into funding problems from private investors and abandoned the trials in 2011. The company’s original plan was to enroll 10 subjects in the study with acute, neurologically complete SCI (just seven-14 days post-injury). Only four received injections of about 2 million cells each. So far, no substantive neurological or functional changes have occurred in any of the enrollees.

The early difficulties of selling the stem cell gamble gave rise to wide-ranging research involving other types of stem cells. In the United States, perhaps the most promising clinical trial today involving humans with SCI are the Pathway trials, which use cells derived from brain tissue of donated aborted fetuses. I asked Dr. Stephen Huhn of StemCells, Inc., the lead Pathway researcher, to explain the difference between embryonic stem cells and fetal neural cells.

“These neural stem cells are multipotent, which means they can only be neural cells,” says Huhn. They do not grow tumors in mice, which has happened with embryonic [pluripotent] stem cells since they can become any type of cell. The risk is much greater with embryonic than multipotent cells.”

From Huhn’s mice studies, neural stem cells were shown to grow into three types of central nervous system cells — neurons, astrocytes, and oligodendrocytes.  “These cells then make neurons and myelin,” says Huhn. “We have seen it in mice trials, microscopically. And the mice, whose spinal cords had been transected, then regained significant ambulatory function.”

From Mice to Humans

OK, enough with the paralyzed mice. We’ve heard their miracle cure stories for decades.

Bring in the humans.

See Also:

 

China Trials Result in Walking

How to Enroll in SCI Stem Cell Trials

The Pathway trials began in 2014 with 12 enrollees, all paras with thoracic injuries from T4 to T11 (seven ASIA A complete, five ASIA B). This was a safety cohort, with no problems reported at the end of one year. Each para received an injection of 20 million stem cells, a tenfold increase from the earlier Geron trials. The StemCells, Inc. website offers further positive info, which can be expected since they hope to attract investors, but is nonetheless encouraging: “Post-
transplant gains in sensory function below the level of injury were demonstrated in half of the subjects. Two subjects converted from a complete injury to an incomplete injury and it has been further observed that one subject with an incomplete injury has shown signs of voluntary toe movement.”

But there was no control group, so the question remains, what improvements might have taken place without the injections? We will never know, but Huhn did admit that the ASIA B group [complete motor and incomplete sensory] “had a better response,” as might be expected.

The good news is the next phase of the Pathway study involves 40 C5-C7 incomplete quads. I spoke with two enrollees of an initial safety cohort who received stem cell injections in March and April of 2015 and had their final evaluations this year. They were excited about their results so far.

Michael Fraser, now 24, injured in July 2013 from a diving accident, went to Shepherd Center in Atlanta for his rehab. While there, his diagnosis was C6 ASIA A (complete) at two months post-injury. By the time he had completed rehab and enrolled in the Pathway study, his diagnosis had improved to ASIA B (complete motor, incomplete sensory), a prerequisite for the study. He had his stem cell surgery (injections) at the University of Pittsburgh Medical Center in April 2015.

“At the time of my surgery, I didn’t have hand or finger function, but I could grasp things weakly using tenodesis (when the thumb and forefinger close together). It was all from lifting my wrist, no finger function. I had no sensation in my legs, no touch, but could feel deep sensation. Now I have much greater sensation and awareness, stronger proprioception [body awareness].”

But what excites him is his overall improvement in strength. “Especially with transfers,” he says. “Before the surgery I was using a transfer board and having difficulty. Always had trouble with my legs, someone would have to grab them and throw them in bed for me. Now I can elevate and transfer without a board and bring my own legs into bed independently, using my wrist under my knee.”

During the trial, participants were evaluated at three-month intervals on a number of practical tests — picking up a key, putting coins in a jar, grasping screws. Prior to surgery he could pick up a key with difficulty but not do anything with it. Progress took time over the course of a year, with noticeable gains between six and nine months. “My balance and arm strength started improving a lot. At the end of 12 months, I could pick up a key and turn it in a lock and pick up coins and put them in a slot.”

Does he think these kinds of improvements might have happened without the stem cell implants? “I definitely feel the stem cells accelerated my improvement, strength and sensation. And one of the things they didn’t measure was the breathing aspect of it. There’s been a very big improvement. I had diaphragm issues with coughing and choking. Now I have a strong cough and sneeze. And I no longer get cold all the time. Whatever the temp is, I’m good with it.”

He sees this as the beginning, not the final result. “I absolutely see myself improving nonstop. I plan on pushing myself every day. Even before the trial I was pushing myself intellectually and physically.”

It will be interesting to check in with him in a couple of years to see if his progress is ongoing.

C4 Quad Makes Similar Gains After Injections

James Mason, injured in April, 2013, was tagged a C4 complete quad at first, but like Fraser, he improved to a C4 ASIA B classification before enrolling in the Pathway trial. He also rehabbed at the Shepherd Center, and in March 2015 received neural stem cell injections at Mount Sinai Medical Center in New York City.

James-Mason
Since stem cell treatment, James Mason has transitioned from a power chair to a manual chair.

“One of the main things was my blood pressure got a lot better,” says Mason. “Before the trials started I used to have to take one pill a day to treat low blood pressure, plus on days when I would be suspended in a harness over a treadmill, I took an extra pill so I wouldn’t get autonomic dysreflexia. At first I would almost pass out. Now I no longer take any BP meds, and I don’t have AD when on the treadmill, and this is with no BP meds. My heart rate is also better, not so slow, so I’m also weaning off that medication.”

Mason also participated in functional tests, like Fraser. Prior to injections, he could not pick up a key from a table. One month later it was about the same. “At three months I was able to pinch it and pick it up but dropped it right away. At six months I picked it up and almost inserted it in the slot. And at 12 months I went further and inserted it, but couldn’t turn it.”

In the last month or two, since his 12-month evaluation, he says he has been getting progressively stronger, with increased sensation. And his bladder control has improved. “Before the trial, when I would clamp off my indwelling catheter, I would not be able to tell when I had an urge to pee, and I would get AD. That would tell me I had to pee. Now I can clamp off my cath and feel the urge to pee when my bladder gets full, so I can unclamp it and pee. Also, before I had to have Botox injections for my bladder every few months. I haven’t had any injections since the stem cell injections.” It’s been more than a year and counting since he’s needed those Botox injections.

One of his biggest improvements, he says, is improved core strength, a major improvement for a C4 complete quad with some sensation. “I’ve always been motivated to work hard, but since the stem cell gains started happening, I’ve been even more motivated.” He maintains a busy workout schedule, working with a personal trainer one day a week on the treadmill harness, and also rowing, crawling and doing assisted pushups and other rehab activities. Wednesdays and Fridays he does FES bike riding for his legs. On Thursdays he does the FES arm bike and the Lokomat.

At home he uses a stim unit on his back and wrists, and he can literally feel the results in his abs. “I can feel my stomach muscles begin to fire with the back stim unit — not normal sensation — but I can feel it happening.”

Perhaps the most practical day-to-day improvement is that he is now transitioning from a power chair to a manual chair. He says he intends to keep working out. “My doctor feels that I may keep making progress for as long as another 10 years or so.”

Other U.S. Human Stem Cell Trials

At least two additional stem cell trials are either underway or have recently been completed. Neuralstem has completed a study on four ASIA A complete thoracic paras, levels T4-T12, all of whom were injected with neural stem cells as of July 2015. Each of the subjects was one to two years post-injury at the time of injection.

In October 2015, Dr. Joseph Ciacci, lead researcher at University of California, San Diego, reported that at the three-month mark there had been no serious adverse events. In other words, the goal of establishing the safety of the trial was apparently accomplished. The study was estimated to have ended by March 2016, with secondary measures of graft survival and immunosuppression results included.

On the functional side of the trial, an exploratory outcome that runs for 60 months (until 2020) will compare baseline and post-transplantation motor and sensory changes, as well as bladder and bowel function.

NEW MOBILITY made repeated attempts to speak with researchers involved in this study. Initial contact with a nurse involved with the study succeeded, but no researcher was available for comment at press time.

A third stem cell trial brings us back to the beginning of this article.

When Geron Corp. suspended its embryonic stem cell trial in 2011, some company employees re-gathered to form a spin-off company, Asterias Biotherapeutics, with the intention of carrying out the aborted Geron trial and going on from there. A new study involving ASIA (complete) C5-C7 quads began in March 2015.

The new trial seeks to enroll 13 subjects from 14 to 30 days post-injury and inject them with from 2 million to 20 million cells from the same source of embryonic cells that had previously been owned by Geron. The safety arm of the trial was scheduled to end one year from injection. Secondary outcomes measuring upper extremity motor levels are to be measured at one, two, three, six and 12 months from injection.

The estimated completion date of the overall study is June 2018.


China Trials Result in Walking

Dr. Wise Young is known for his involvement with SCI communities both in the U.S. and around the world.
Dr. Wise Young is known for his involvement with SCI communities both in the U.S. and around the world.

One of the most respected SCI researchers, Dr. Wise Young, has been involved for many years with organizing and overseeing research protocols and trials in China and other countries. As of the writing of this article, very promising trial results involving implantation of umbilical cord blood mononuclear cells [UCBMNC] into people with chronic complete injuries were in the process of being published in the journal, Cell Transplantation. NEW MOBILITY will publish a full feature article on this most recent work of Young in our July Issue.

In the meantime, Young, in a letter sent in May from the Keck Research Center, his academic and research home in New Jersey, reports the exciting and unexpected results of the trials.

Eight subjects in Hong Kong with chronic complete SCI received injections of 100,000 UCBMNC above and below the injury. None of them recovered motor function, but imaging of the spinal cords suggested that at least two had fibers that regenerated across the injury and the trial showed the transplants were safe. In the second part of the trial, in Kunming, 20 subjects received similar UCBMNC treatments but also underwent extensive locomotor training six hours a day, six days a week, for three to six months.

Young went on to write:

“At one year after treatment, 75 percent (15/20) of the subjects in Kunming recovered the ability to walk long distances in a rolling walker with minimal assistance (If necessary, a person walked behind with ropes tied to the legs to prevent the knees from buckling.) Thirty-five percent (7/20) could walk without such assistance using either a four-point walker or crutches. … When they went home, some of the subjects 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 subjects 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,” Young said in discussing the results with NEW MOBILITY. “We believe that there’s an important lesson to be learned in the two papers. The stark difference between recovery in Hong Kong versus the recovery in Kunming, we believe, is due to the presence of the intensive walking program. … In other words, if you don’t exercise and do intensive walking training, you will not recover any function no matter what you transplant in.

“That’s the point of our paper, and I think it’s a very important lesson. In fact, it really opens up the question whether more therapies would work if people actually trained.”


How to Enroll in SCI Stem Cell Trials

Stem cell trials for people with SCI are still in the relatively early stages of development. In addition to the three studies listed below (one currently closed), a new study based on Dr. Wise Young’s trials in China with umbilical cord blood cells will begin in the United States as early as the end of 2016, but more likely in 2017. For more on this see our July issue.

Current Trials
• Asterias Biotherapeutics (SCiStar, C5-C7 complete, 14-30 days following injury). Study is ongoing and recruiting at six locations in United States. For specific locations, go to: tinyurl.com/zv6po2p; asteriasbiotherapeutics.com/

• Neuralstem Trials (T2-T12 chronic complete SCI): Study is ongoing but not currently recruiting subjects. No test results have been reported as of mid-May 2016. For more info go to tinyurl.com/hr35vmqwww.neuralstem.com/cell-therapy-for-sci

• Hundreds of clinical trials involving SCI have been or still are ongoing in areas other than stem cell research. For a current, complete list of U.S. SCI Studies, open and closed, all types, go to: tinyurl.com/zsagpq8.


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