Stem Cell Therapy Reaches Human Patients

by Guy McKhann, M.D.

February 11, 2009

Two recent articles highlight the potential importance of stem cells in future treatments of neurological diseases. The Proto Magazine article “Fertile Ground” summarizes where things stand in the field of regenerative medicine—that is, attempts to repair brain circuits using replacement tissues such as stem cells. The Los Angeles Times article “Stem Cell Therapy to Be Tested on Spinal Cord Injuries” reports that the Food and Drug Administration (FDA) has approved a trial to use embryo-derived stem cells in the treatment of spinal cord injury, the first time human stem cells will be used to treat humans.

Stem cells are derived from early embryonic tissue and have the potential to differentiate into any of the 200 different cell types in the body. (We use the term “differentiate” to describe the process by which an immature cell changes into a more stable mature cell). The biotech company Geron, which will conduct the study mentioned by the Los Angeles Times, has been in the business of trying to apply human embryonic stem cells to human disease since just after the discovery of stem cells in 1998. Now, 11 years later, they are finally able to test such an application.

Several steps were necessary to reach this point. Perhaps most important, researchers had to take these primitive, immature cells and coax them into differentiating into a specific brain cell type. The Geron scientists didn’t try to make a nerve cell. Rather, they made a highly specialized cell called an oligodendrocyte (an “oligo”). These cells make the insulating material around a nerve fiber. Called myelin, this material acts like the insulation on a wire conducting electricity. When disrupted, the neuron fails to transmit the message, much as an electric current would be disrupted by faulty insulation. In animal models of spinal cord injury, such as studies conducted on rats, injecting a mixture of oligos and oligo precursors into the damaged spinal cord resulted in more myelin formation and recovery of motor function. And despite some concern, these cells did not differentiate into tumors. Thus the stage was set for review and approval by the FDA for use in humans.

The studies ahead

The next step will be to recruit research centers with a track record in treating spinal cord injury. The plan is to treat 10 patients seven to 14 days after the injury with a single injection of cells into the damaged spinal cord and then follow the patients for a year, or longer. This study is designed to ensure that the treatment is safe, but clinicians will also be looking for any signs of improvement.

The Geron researchers were wise to start with spinal cord injury, for which we have no effective therapies. They were also wise to choose a specific cell type, the oligo, with a specific function, to make myelin. Trying to make replacement nerve cells is much harder. Neurons have many different specific functions, and trying to replicate these functions is a real challenge.

However, even using oligos may not be that simple. If recovery occurs it might be because the implanted cells made new myelin, but there are other possibilities. These cells also produce substances that promote brain recovery, which can be released locally, at the site of injection. The mechanism of any effectiveness, if it occurs, will have to be explored in further animal experiments.

Where does all this leave us in relation to using stem cells to treat other neurologic problems, such as Alzheimer’s, stroke or Parkinson’s? There are other forms of stem cells, more differentiated than the immature ones from human embryos. These so-called “adult stem cells” also have the potential to differentiate but are already somewhere down the path to the ultimate cell type. Thus one can obtain “neural stem cells” that already exist in the brain and are destined to differentiate into various types of brain cells, and place them in the injured brain to promote recovery. Interestingly, almost at the same time as the FDA approval for the spinal cord injury study, British regulators approved a safety trial for using neural stem cells to treat stroke.

In the United States, the stem cell field has been held back by restrictions imposed on the use of embryonic stem cells in government-sponsored research. Those restrictions are now being lifted. Researchers who once relied on support from private industry or state programs will now be able to apply for federal funding. There is still a far distance to go, but the long-awaited first steps toward widespread stem cell therapies are about to take place.