2013 - Year of the Stem Cell


Pioneer Founding member
2013 - Year of the Stem Cell


Marcus Hilton has probably been going blind since he was born, though he didn't really begin to notice that something was wrong until he was seven or eight. Several years after that, he was officially diagnosed with Stargardt disease, the leading cause of juvenile blindness. Thirty-four years of decline later, his retinas irreparably damaged, he is unable to drive, read fine print, or recognize people from a distance.

For Knut Olstad, devastation came much more suddenly. Having quit smoking and taken up cross-country skiing and bicycling in an early mid-life crisis, he was 45 years old and on what he described as the vacation of his life, conquering 25 mountains on the Tour de France route. On the last descent of the twenty-fifth mountain, on what might even have been the final turn of the entire trip, a car veered into his lane. He swerved out of the way, squeezed just a little too hard on the front brake ... the next thing he remembers is waking up, immobile, in a hospital where equipment beeped ominously through his morphine fog and everyone spoke a foreign language.

"I thought I was in a science fiction movie," he recalled over the phone from his home in Norway. And even as he's slowly been able to make sense of what happened to him, his life since then has, in a way, remained in the realm of the abnormal.

In 1998, when human embryonic stem cells were first isolated, we anticipated a "rush of medical advances," as The New York Times put it. That promise -- along with all of the ensuing controversy -- is still alive, has already become reality in select cases -- for example, with bone marrow transplantations -- and still has plans to live up to all of the expectations that have been set for it.

"The question now," the Times wrote then, "is what use can be made of the potentially awesome power to rejuvenate human cells." After 15 years, there are a lot of people waiting for a miracle, for the day cell-based therapy gives back what's been taken from them.

People blind from macular degeneration, like Hilton, who's blind "on paper only" but hopes that research will forge ahead to help not just him, but everyone suffering from degenerative diseases.

People with spinal cord injuries, like Olstad, who is still struggling to come to terms with the fact that he had just turned his life around when life, in turn, put him in a wheelchair.

People losing their minds to Alzheimer's, and their bodies to Parkinson's and ALS. People with heart disease, diabetes, and cancer; children with genetic brain disorders who aren't expected to live to see their tenth birthday.

Stem cells were only quietly on the radar in 2012. In October, the Nobel Prize was awarded to John Gurdon and Shinya Yamanaka, who are lauded for laying the foundation of regenerative medicine, for work done, in Gurdon's case, in 1962, and, for Yamanaka, more recently in 2006. In the labs, those on the front lines of stem cell research have seen important results: the first preliminary data on a clinical trial at UCLA with embryonic stem cells was published at the end of January, funded by the company Advanced Cell Technology (ACT). In September, the first data from neural stem cells being used in human spinal cord patients in a hospital in Zurich was presented by StemCells, Inc, and in October, the company published data from a second trial in children with a fatal disorder affected their brains' myelin production -- the first trial, which was also the first to receive FDA approval to transplant neural stem cells into children, took place in 2006.

The findings come from two different areas of the field: ACT works with what are known as pluripotent stem cells, which can be made to turn into any cell in the body. StemCells, Inc., on the other hand, uses tissue-specific, or "adult," stem cells, which have already become what they are -- in this case, brain tissue.

And the progress, thus far, looks something like this: Knut Olstad could feel a finger placed on his stomach almost 50 percent of the time, and brain scans of electrical stimuli back up his assertion that some feeling has indeed been restored to where previously, there had been none.

Three of the six children from the first neural stem cell trial have since died from their disease, but autopsies showed that the stem cells survived and migrated throughout their brains. Children in the second trial have been making modest gains, and their cells are creating new myelin, as they're intended to.

The small area of Hilton's retina that was injected with pigmented cells at Moorsfield Eye Hospital in London has retained that pigmentation after 16 months, meaning the cells haven't been rejected. Some of the two dozen similar patients are saying they can see purples and blues again.

It's small and non-definitive progress, yes, and researchers have done their due diligence not to overinflate reality. The press has been similarly subdued, hinting only at signs of "potential." But when Hilton and Olstad signed up to participate in clinical trials, their doctors were extremely cautious not to make any promises. The men, after all, were both taking part in safety trials -- the goal was only to see whether hundreds of thousands -- or in Olmstad's case, millions -- of stem cells could be injected into human subjects without tumors forming, for example, and without the patients being harmed by the immunosuppressants they're required to be on. They were chosen to participate precisely because of how absolute their disabilities were. For something to go right -- for any improvements in their conditions to be seen at all -- was not part of the plan.

But Olstad said that although he knew not to expect anything, he still had hope. "Otherwise," he said, "I would not have participated."

StemCells Inc. is currently performing more safety trials at the University of Zurich in patients paralyzed by spinal cord injuries. Of three patients, two have regained some sensation below the level of their injury. The full results will be published early in 2013, after which they can begin testing in patients with milder injuries -- patients for whom a dose of stem cells could improve their partial functioning. For the first time, explained Stephen Huhn, the company's vice president, neuroscientists can actually look at the possibility of being able to repair the central nervous system.

For the macular degeneration trials, the goal isn't to restore vision to the blind, but to prevent disease-related degeneration to begin with. Since they haven't seen any adverse effects in their trial patients, explained Robert Lanza, the chief scientific officer at ACT, they're moving to inject stem cells into patients at much early stages of disease who still have relatively good eyesight, with the goal of keeping it from getting any worse. In a different approach to the same condition, StemCells, Inc. has also initiated a trial that uses neural stem cells in patients with dry age-related macular degeneration.

In all future trials, ACT will also be using its patented "embryo-safe" technique, which allows them to biopsy a single cell from an embryo -- similar to what's done in pre-implantation genetic diagnosis during the IVF process -- and then replicate that cell ad infinitum. Lanza, whose accent renders him unequivocally Bostonian, was all but obligated to put it this way: "If you consider that cell to be one Red Sox fan, we can actually, from there, create enough to fill all of Fenway Park."

They're also in the process of filing with the FDA to begin trials with platelets derived from pluripotent stem cells, as an alternative to the embryonic blood transfusions currently in use. After establishing safety, the next phase, which would begin sometime in the first half of 2013, will use blood or skin cells derived directly from the patient -- who would then become his or her own blood donor, and thus eliminating the need for transfusions.

"The field is advancing, and like everything in medicine, it takes time," said Huhn. He compares it to the moon landing -- before there was one small step for man, there were countless smaller steps leading up to that moment. His company is now underway in planning a phase II controlled trial for the fatal childhood myelination disorder -- meaning they'll be able to evaluate stem cells' potency as a treatment -- and they are also seeking approval to conduct trials in patients with Alzheimer's, which animal data suggests could be effective.

Indeed, animal trials are where most progress has thus far been seen; most recently, the composite results of eleven independent mouse studies lead experts to conclude that the transplantation of neural stem cells into patients with ALS, with the goal not to cure, but to sustain life, "may be ready for clinical trials."

"This is a field that has received a lot of attention -- some would even say hype -- and I think that expectations about how quickly we can do things have been raised," Huhn added. "But I feel good that even though it looks like we're proceeding incrementally, that we're starting to accelerate and get more interesting data."

"We're trying to move as responsibly as we can, but we are going to accelerate it seeing as we haven't had any adverse effects with the patients that were treated to date," said Lanza, adding that it was difficult to say no when the first macular degeneration patients begged them to defy protocol and treat their second eye. "If we have something we can do to help these patients, we really have an obligation to move this along as expediently as we can."


It's Not Too Early to Talk About Freezing Your Eggs
2013 probably won't be the year that the big miracles anticipated from stem cell research will come to pass. But it does promise to be one full of more small, but significant advances toward that future goal.

In the meantime, Hilton sits in front of his TV, covering and uncovering his treated eye while he watches the news ticker at the bottom of the screen, noticing small differences in the size of the text. Olstad, from his wheelchair, works out every day, imagining that he can somehow encourage the stem cells implanted above the site of his injury to connect with those implanted below.

"I feel very strongly about the obligation to be balanced and measured, but also to convey that we're starting to make progress," said Huhn. "It's this type of work that leads to medical breakthroughs."