You've heard of stem cell therapies being used to cure or at least partially restore mobility in animals with damaged spinal cords. But what about in humans? Now there are two studies underway. Here's how close we are to seeing humans released from paralysis thanks to stem cells.
Although not all spinal injuries cause complete loss of function, they still often require a huge adjustment in a person's life. Finding some way of curing, or at least partially ameliorating the effects of severe spinal cord injury has been a dream of many. When stem cell therapies began to be a possiblity, those dreams got a lot more tangible. Early testing showed that some mammals, at least, could recover from paralyzing injuries with the use of stem cell therapies.
Unfortunately, there are a lot of people willing to cash in on people's willingness to try anything to treat such injuries. Some time ago, The Shepherd Center for Spinal Cord Rehabilitation posted a notice; "Of Spinal Cord Injury, Stem Cells, Snake Oil, and Serious Hope," about the number of people offering stem cell trials which were not done under the oversight of any regulatory body, and had no scientific basis. Often patients would pay through the nose, only to lose mobility in still-functional body parts after receiving treatment. What's more, past treatment disqualified patients for new and more legitimate studies. There were more conmen the legitimate clinicians offering treatment. It looks like the balance is changing. In October of last year, The Shepherd Center and Geron Corporation announced their own new trial using stem cells to treat spinal cord injury.
The trial is in Phase I clinical testing, which means it is not yet being assessed for effectiveness, but for safety. The study is registered on the National Institute of Health's site, where the goals are spelled out. The secondary goal is improved sensation and movement in the extremities. The primary goal is evaluating the treatment's safety, "as measured by the frequency and severity of adverse events within 1 year (365 days) of GRNOPC1 injection that are related to GRNOPC1, the injection procedure used to administer GRNOPC1, and/or the concomitant immunosuppression administered."
This is normal for Phase I testing, which is usually done on perfectly healthy people to see how they process the drug. Geron and The Shepherd Center declined to comment on how the study was progressing, but there are some signs. For one thing, the study has not been cancelled yet, despite six months of testing, so whatever adverse events or immunosuppression that patients have experienced has not been to severe or discouraging. What's more, the study is expanding. The NIH tracks any changes in studies, and so far there have been two. Work was done at Northwestern in Illinois at first, then included Stanford in California on January 25th, and then the Shepherd Center in Georgia on February 10th.
The study is being conducted with the most controversial cells in modern science, human embryonic stem cells. The ones used in the study were taken from embryos which were harvested for in vitro procedures and given to science by the biological donors. They were undifferentiated, until treated with biological agents that created a group of cells containing oligodendrocyte progenitor cells, or OPCs. The name used for the stem cell formulation, GRNOPC1, denotes that the OPCs are made and mixed by Geron(GRN). Oligodendrocytes both manufacture proteins that heal and enhance nerve cells, but they also produce myelin. Myelin wraps around nerve cells and allows them to send signals efficiently and quickly.
Many spinal injuries are caused not by the severing or cutting of the spinal cord, but by simple bruising or crushing. The oligodendrocytes become damaged by the inflammation of the cord. These injuries leave lesions - neurological dead zones that cause paralysis. It is these lesions that the study is hoping to repair with GRNOPC1 injections. Right now, the testing if very limited. Researchers are only looking for patients with crush or bruising injuries, not any injuries due to penetrating trauma. They also are using patients with only a single lesion and with complete paralysis, no motor function or sensation below the injury. Finally, they're only taking patients who have been injured in the last seven to fourteen days. The stakes are high, and any progress has to be measurable.
This phase of the study has been a long time coming. GRNOPC1 was initially tested on animals with these type of injuries back in 2005. When the animals showed improved motor function and when the spines of such animals were found to have increased numbers of nerve fibers and those nerve fibers were re-covered with myelin, the results were published in Journal of Neuroscience. Of course, it doesn't just have to work, the animals have to survive it working. Animals on which these were tested were examined for teratomas - tumors - in the injection region, cysts, and for increased pain. Although no pain or tumors were found, some small cysts did show up in the injection areas. Those cysts were smaller than the injury site itself, and didn't seem to affect the animals, which was what led to the test in progress, being cleared for humans.
This is exciting news, and what's more exciting is that Geron may well have some competition. Japanese scientists recently healed monkeys using induced pluripotent stem cells (iPS) cells. These cells are made from the skin, and induced to become stem cells. Though the monkeys recovered in a matter of weeks, their injuries were only sustained a few days before. Induced stem cells take a long time to make, during which the amount of time the opportunity for an injured person to benefit from such an injection may pass. There's even another Phase I clinical trial to use stem cells to heal spinal cord injuries out there. TCA Cellular Therapy started a Phase I clinical trial of bone marrow derived stem cells in September of 2010, and this one is looking for people injured more than two weeks prior. The fact that so many likely sources for treatment of spinal cord injury exist is cause for great excitement. As testing continues, we can hope that more progress is made. The average drug study takes eight years, from initial application to marketing. If these treatments do well, paralysis due to traumatic spinal injury may be a treatable condition by 2020.
Many thanks to Robert Gonzalez, the hardworking io9 intern who helped with research!