Last week, a California biotech company announced that its human stem cells restored memory in rodents bred to have an Alzheimer’s-like condition—the first evidence that human neural stem cells can improve memory.
The company, called StemCells, is betting that its proprietary preparation of stem cells from fetal brain tissue will take on many different roles in the central nervous system. The company and its collaborators have already shown that its stem-cell product has potential in protecting vision in diseased eyes, acting as brain support cells, or improving walking ability in rodents with spinal cord injury.
This metamorphic ability is not so surprising—they are stem cells, after all. But experts say the quality of scientists involved in StemCells and the interesting properties of its cells sets the company apart. “They’ve really been steadfast in their work to get these cells into clinical trials. That is a tough road and they’ve done it,” says Larry Goldstein, a neuronal stem-cell researcher and director of UC San Diego’s stem-cell program.
The company discovered the technique to isolate these cells from brain tissue in 1999 and has since spent some $200 million improving the technology. “Now we are really in the exciting phase, because now we are looking at human clinical data, as opposed to just small animals,” says StemCells CEO Martin McGlynn.
His company is not the only group bringing stem cells into the clinic. While much attention was paid to Geron’s departure from the world’s first embryonic stem cell trial (see “Geron Shuts Down Pioneering Stem-Cell Program”), many other groups have continued to push their non-embryonic stem-cell therapies forward for leukemia, colitis, stroke, and more. Meanwhile, Advanced Cell Technology continues its U.K.-based embryonic stem-cell therapy trials for blindness. Non-embryonic stem cells can come from a variety of sources—bone marrow, blood, as well as donated aborted fetal tissue, as is the case with StemCells and Neuralstem, another company focused on neuronal stem cells. In recent years, scientists have also developed methods for turning normal adult cells into stem cells (so-called induced pluripotent stem cells), but their safety has yet to be tested in humans.
So while StemCells is not a lone wolf, it may well be a pack leader. One of StemCells’ first human studies involved a small trial of young children with a rare and fatal neurodegenerative disease called Batten disease. In 2006, the company began the first U.S. Food and Drug Administration-authorized trial of human neural stem cells at Oregon Health and Science University. Through small boreholes in the skull, a neurosurgeon implanted as many as a billion neural stem cells into different locations of the brains of six Batten patients.
The trial has since suggested that the cells are safe and integrate into the brain. At first, the children received immune system-suppressing drugs to prevent their body from rejecting the cells. But after a year, that treatment was stopped. “A big question that we had, that science had, that the FDA had, was what happens to these cells when you withdraw immunosuppression?” says McGlynn.
The treatment, however, did not rescue the children from the effects of the disease, and some have since succumbed to the disorder. Some of the parents of the children who passed away gave permission for an autopsy, enabling the scientists to see that even after one and a half years with no immunosuppression, the transplanted cells had survived. The company wanted to try the cellular therapy in children at an earlier stage of the disease, but was unable to find eligible patients at such a point in the disease course and canceled the trial.
In another small trial, the cells have shown the ability to make functional changes in the human brain. At the University of California, San Francisco, four children with a genetic disease that prevents their brains from producing myelin—the insulating sheath on neurons that is necessary for proper electrical signaling—received the cellular treatment. In StemCells’ study, three of the treated boys had small but measureable gains in neurological function, while the fourth remained stable. MRI scans indicate that the boys’ neurons have gained more myelin sheaths, which remain even after immunosuppression is removed.
The company has also initiated trials in patients with spinal-cord injuries and macular degeneration, a disease of the eye that gradually destroys central vision. Its Swiss-based trial with spinal-cord injury patients, begun in 2011 at the University of Zurich, has so far enrolled three patients, two of which have reported changes in their sensitivity to touch. These patients each received a direct transplant of 20 million stem cells into the spinal cord. Last month, the company also announced the beginning of a trial for dry age-related macular degeneration, for which there are currently no FDA-approved treatments. A trial at the Retina Foundation of the Southwest in Dallas will test stem cells in the eyes of up to 16 patients.
But even with years of solid lab animal data and promising first starts in humans, success is no guarantee. “Animals only tell you a subset,” says Goldstein. “Who knows what’s going to work for which disease. When you get to clinical trials for people, all bets are off.”