Non-Embryonic Stem Cells: Political Changes and Scientific Advances
Attention shifted away from ACT. Instead, everyone started talking about Geron, another biotech company on the West Coast. Researchers there had succeeded in cultivating nerve cells from embryonic stem cells. With support from Christopher Reeve, the paralyzed “Superman,” there was renewed hope that spinal cord injuries could be healed. Three patients were treated using the therapy developed by Geron. But in November 2011, the company put the brakes on the research due to a lack of funds.
That was the moment when Lanza realized that he once again had to play the role of stem-cell-research poster boy. But this time he had something to show for his efforts. Benefiting from progress that Geron had made, ACT had also managed to gain FDA approval for a clinical trial.
Researchers had cultivated so-called retinal pigment epithelium (RPE) cells, which form a thin layer over the retina and keep the photoreceptor cells nourished and healthy.
In July 2011, doctors at the University of California in Los Angeles (UCLA) injected the first two patients directly behind the retina, each with some 50,000 RPE cells from Lanza’s cell factory. There are now 36 patients in the US and the UK taking part in the trials. They either suffer from the hereditary Stargardt disease or age-related macular degeneration (AMD), both of which are conditions in which RPE cells slowly die, resulting in a loss of vision.
Initial Success and Tempered Optimism
One of the Stargardt patients is David Lee, from the northern English town of Leigh, just outside of Manchester. Following a routine eye checkup 25 years ago, Lee was told that he suffers from the disease. Over the ensuing years, he has had to idly stand by while he progressively loses his eyesight. “Watching television has become very hard, and reading is impossible without magnification,” the 47-year-old says.
Then Lee heard about the stem cell trials and submitted an application to become a subject in the study. In late July 2012, he was operated on by a team working under surgeon James Bainbridge at Moorfields Eye Hospital in London. The doctors injected RPE cells in Lee’s left eye. “I was exceptionally happy about it,” he says.
Lee regularly travels to London to have his eyes examined. His physicians are satisfied. The RPE cells from the bio lab are thriving in Lee’s retina. “I see definitely brighter on the eye that was operated on,” he says.
He runs a bakery out of a small brick house in the center of Leigh, and he can still see just well enough to be able to sell cakes, pastries and bread. “I know that I won’t get my sight back”, Lee says. “But, for me, it would already be a big success not to lose any more of my sight.”
Many of the patients report that the therapy is effective. “We have some surprisingly good visual outcome,” says Steven Schwartz, an eye surgeon at UCLA. He says that one of his patients can read a clock again and go shopping, while another can recognize colors again. In addition to AMD and Stargardt patients, Schwartz plans to integrate extremely nearsighted individuals into the test program soon. The FDA has already approved the clinical trials.
Lanza is a “genius” and his work is “stellar,” Schwartz says. “The patients seem to tolerate the cells well,” he says. But the researcher warns against overly optimistic expectations, adding that it remains completely uncertain whether the innovative eye therapy will actually heal these ailments. He notes that the trials are mainly meant to test the safety of the procedure.
Stem cells can transform into virtually any type of body cell. Once they have become differentiated, they tend not to cause any problems. But what happens if they continue to develop, and one of the RPE cells from the lab mutates in the eye and becomes malignant?
“I worry that a single case of cancer in a stem cell model like this could set the field back enormously,” says Arthur Caplan, a bioethicist at the University of Pennsylvania. He is concerned that ACT may be pursuing its clinical trials far too aggressively. After all, the company has to placate its investors and outdo the competition.
Competitors and Risks
Indeed, Lanza will have to hurry up if he wants to be the first to come up with a clinically tested application for iPS cells. His greatest rival is located in Kobe, Japan, at the RIKEN Center for Developmental Biology. There, Dr. Shinya Yamanaka is working on groundbreaking stem cell therapies.
And the Japanese researcher is a very capable contender. After all, he received the Nobel Prize in physiology or medicine last October for his method of producing iPS cells. Like Lanza, Yamanaka is striving to use stem cells to cure blindness from macular degeneration (AMD). But, unlike Lanza, he plans to use iPS cells.
“Lanza is under tremendous pressure to show some positive results,” Caplan warns, adding that he is without a doubt a serious researcher. “But ACT has a history of overselling. They made a lot of promises in the past that just haven’t delivered.”
Lanza is aware of the bad press. “Mistakes have been made,” he admits. But he remains feisty. For instance, he accuses Yamanaka, his Japanese counterpart, of venturing an experiment that is particularly risky. “We still don’t entirely understand how safe iPS cells are and how they work,” says Lanza. Using them to cultivate RPE cells to treat eye diseases is dangerous, he adds, because the cells could possibly become cancerous in patients’ eyes.
“By contrast, we picked platelets for our first clinical trial with iPS because they have no nuclei,” he says. There is no chance of them growing out of control.
Enthusiastic about the Future
“Come have a look, I’m going to show you something else,” Lanza says at the end of the interview, as he opens a binder and pulls out a diagram that charts age relative to degree of paralysis. It has to do with multiple sclerosis. Lanza has studied mice that suffer from this crippling neurological disorder. The curve documents the sad fate of untreated animals: At the age of two, they drag their hind legs behind them. At the age of three, they are completely paralyzed.
But it’s a completely different story among the mice that were treated with stem cells: The curve of this group can hardly be differentiated from that of healthy animals. “One shot of these cells and they are jumping around completely normal,” Lanza says with enthusiasm. The researcher treats the animals with so-called mesenchymal stem cells (MSCs), which are cultivated from embryonic stem cells or iPS cells. They resemble bone marrow cells and secrete substances in the body that work like a fountain of youth.
“That’s the future,” Lanza says. He points to an entire list of diseases that could potentially be treated with MSC cells, including chronic pain, arthritis and Parkinson’s. “The biological potency of these cells is just incredible! And we can make them by the millions,” he exclaims.
This is what Lanza is like when he’s in the grips of enthusiasm. His eyes sparkle and his gestures underscore each word. At moments like these, one senses how far his enthusiasm can take him.
“Before ACT hired me, they gave me a task,” he explains. “I was asked to get all the Nobel laureates in the country to sign a letter to support embryonic stem cell research.”
Lanza put his fax machine to work. Ever since then, he has had a stack of letters in his desk drawer — with the signatures of 70 Nobel Prize laureates.
By Philip Bethge