Chronic Trials: 2015 A Banner Year

Posted by Sam Maddox in Research News on December 25, 2015 # Research

A year-end look back at spinal cord injury research: by at least one yardstick, it was a very hopeful year. There were an unprecedented number of clinical trials for individuals with long-term SCI.

The Big IdeaFirst, the epidural stimulation studies at the University of Louisville have continued beyond the first four participants we’ve all come to know – these are the four amigos who were all motor complete injuries, and who got back voluntary control of paralyzed muscles when the stimulation was on. They also got health benefits from some autonomic recovery, including better bowel, bladder and sexual function.

Under the direction of Susan Harkema, the center has now performed epidural implants on a total of ten patients. Neither the researchers, nor patients, are revealing anything about the latest six except that they appear to be responding consistently with the first four. That sounds like code for good news. The first subjects have all been men. The next two will be women.

Meanwhile, The Big Idea, the Reeve Foundation trial initiative, expects to start enrolling patients in the coming months, once administrative and regulatory issues are locked down. This trial will implant stimulators (the same units as in the earlier studies) in 36 more individuals with chronic spinal cord injuries.

At UCLA, where Harkema trained under Reggie Edgerton, stimulation experiments are underway in his lab on individuals with injuries from two to six years, this time using a stimulator that requires no surgery. Edgerton’s group reported that five men with motor complete spinal cord injuries improved voluntary “locomotor-like” function after the transcutaneous stimulation experiments. Certainly nonsurgical treatment has its appeal (cheaper, safer) but Edgerton notes that the external stimulator, being developed by a company he formed (NeuroRecovery Technologies), won’t supplant the surgical units. The idea, he says, is to build the most robust toolbox possible and adapt it to specific patient needs.

In a parallel spinal cord stimulation study at the Edgerton lab, Reeve Board member Mark Pollock was treated with spinal cord stim (transcutaneous – no surgery) combined with buspirone, a drug that stimulates the spinal cord; he also employed a robotic exoskeleton. This combination enabled Pollock, a complete paraplegic, to assist the robot in moving his legs; he was able to actively flex his left knee and raising his left leg when the stim was on.

Regular readers know we pay close attention to SCI stem cell trials. Recently, StemCells, Inc. reported (in advance of peer review or publication) that five of six motor complete quads treated with neural stem cells long after their injuries recovered strength in their hands. Three treated patients were able to pick up a key, put it in the lock unlock it.

StemCells calls its study Pathway; they are now recruiting patients for a second phase -- 40 patients with C5 – C7 injuries (incomplete) between four and 24 months post injury, at 12 centers in the U.S. and Canada.

Neuralstem completed a safety trial of its neural stem cells in four patients with chronic spinal cord injury (thoracic) at the University of California, San Diego School of Medicine. The company expects to resume implanting cells once Phase 1 safety data gets locked down. The company reported a few weeks ago that the cells were well tolerated and that no adverse effects were seen.

Without a lot of fanfare, the Miami Project began a trial in October implanting Schwann cells in patients a minimum of one year post injury. The Schwann cells are harvested from the patients’ own sural nerve, in the calf, and of course part of the peripheral system. Schwann cells help repair damaged peripheral nerves by replacing myelin insulation. Those in the Miami trial also receive fitness conditioning and rehab before and after cell transplants, this so they are as healthy as possible, and also to promote any potential for activity based neuronal plasticity (nerve growth). Trial enrollment targets two cohorts, thoracic and cervical.

This, from the SC trial posting on

For humans with chronic SCI, we hypothesize that axons might show improved function if myelin repair is induced with the implantation of ahSC [autologous human Schwann cells]. In addition, spinal cord cavitation may be reduced, and neural sprouting and plasticity may be enhanced via neurotrophic effects.

Participants will be monitored throughout a 6 month post-transplantation evaluation period for occurrence of AEs (adverse effects, acute, delayed, and/or cumulative), as well as for changes in clinical status and neurological status. Safety and efficacy assessments will be performed at weeks 1 and 2 post-transplantation and months 2 and 6 post-transplantation.

The Miami group has been working on Schwann cells for decades. They know from animal models that the cells do indeed facilitate axon recovery in the cord. They also know that SC alone will not lead to significant recovery – axons that respond to SC don’t leave the lesion site without some help. The answer is in combining SC with growth factors, bridges, scaffolds, etc. The FDA requires testing one thing at a time, so once safety is assured, the Miami group will likely move toward combo trials.

James Guest, a doctor-scientist at the Miami Project, and a Principal Investigator in the Reeve North American Clinical Trials Network, told me that his group is already doing preclinical SC combinations with animal models. Interestingly, he noted that SC epidural stimulation seemed to have a nice effect in a large animal model (pig). Guest said he’s also working on primate studies, genetically inducing expression of chrondroitinase [a bacterial enzyme that breaks up spinal cord scarring] in combination with Schwann cell transplants.

Note: this article did not cover overseas trials or several small clinical trials in chronic SCI using various types of brain/computer interfaces, electrical stimulation or magnetic stimulation. To keep abreast of those and all other NIH-registered clinical trials in the spinal cord injury field, be sure and see Spinal Cord Outcomes Partnership Endeavor (SCOPE,, which highlights trials for both “Rehabilitation and Technological Interventions,” and for “Drug, Cell, and Surgical Interventions.” Dan Lammertse, a physician from Craig Hospital in Denver, compiles and updates the SCOPE data.

The National Paralysis Resource Center website is supported by the Administration for Community Living (ACL), U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling $8,700,000 with 100 percent funding by ACL/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by ACL/HHS, or the U.S. Government.