Taking root. Three months after they were injected, dark RPE cells (bottom) can be seen in the eye of this patient with Stargardt macular dystrophy.

Adapted from S. D. Schwartz et al., The Lancet, Online Publication (January 23, 2012)

Embryonic Stem Cells Appear Safe, May Help Eye Disease

In the first published results from a clinical trial using human embryonic stem cells, two legally blind patients who received an injection of hESC-derived cells in one eye have experienced no harmful side effects and appear to have slightly better vision. Although the result is preliminary, it is an important milestone for the struggling hESC field.

Since their discovery 13 years ago, hESCs have shown great promise for treating diseases, but they have also been dogged by safety issues and ethical concerns because deriving the cells often destroys human embryos. In the only ongoing clinical trials involving hESCs, the biotechnology company Advanced Cell Technology (ACT) of Marlborough, Massachusetts, derived a type of cell called retinal pigment epithelium (RPE), which sustains the retina's light-sensing photoreceptors. Collaborators at the University of California, Los Angeles, then used these cells to treat an elderly woman who has dry age-related macular degeneration and a woman in her 50s who has Stargardt macular dystrophy, a rare inherited disease. The researchers injected 50,000 RPE cells suspended in a solution under the retina in one eye of each patient.

Four months after receiving the treatment, the patients have not developed any tumors or abnormal growths that have sometimes been seen in animals receiving hESC-derived cells, the team reports online today in The Lancet. The patients, who received immune-suppressing drugs for 12 weeks to prevent their bodies from attacking the cells, also have not shown inflammation or other signs of rejecting the cells.

The researchers detected RPE cells in the eye of the patient with Stargardt disease but not in the patient with age-related macular degeneration. However, both women's vision seemed to improve, particularly in the patient with Stargardt. She went from seeing only hand movements to being able to read a few letters on an eye chart. The authors caution, however, that measuring small visual improvements is difficult and that they can't say for sure that the changes were not the result of the immune-suppressing drugs or a placebo effect.

"It's a long time coming. It's rewarding to finally see years and years of research translated to the bedside," says Robert Lanza, CEO of ACT.

Other hESC researchers welcome the report but caution that the study was very small and designed only to test the safety of the procedure. "This is a major milestone that will offer tremendous encouragement to the field and [that] promises hope for many families," stem cell researcher George Daley of Harvard Medical School in Boston writes in an e-mail. "But these are still very early days, and we have much more to learn about the safety and effectiveness of this new treatment before we can claim success."

Peter Coffey of University College London's Institute of Ophthalmology, who is working on a similar treatment for macular degeneration, says the safety results look "very good." An immune reaction is less likely in the eye than in other sites in the body, and animal studies have suggested the RPE treatment should be safe. But "you never know until you go into the clinical setting," Coffey says. He declined to comment on effectiveness of the treatment until the trial is completed.

Coffey is part of a trial sponsored by the drug company Pfizer awaiting approval in the United Kingdom that will slip a patch of hESC-derived RPE cells under the retina instead of injecting them in a liquid suspension. "We think it will work better" because RPE cells naturally form a single-cell layer, like a carpet, Coffey says.

The ACT trial continues: Collaborators in the United Kingdom treated a third patient Friday. The company plans to inject various doses of the cells into a total of 12 patients in each trial. "Things will accelerate" now that the treatment appears to be safe, Lanza says. If the trials go well, the company will then seek to treat younger patients who should benefit more from the treatment.

Supporters of hESC research were devastated last November when Geron, the California biotech that was conducting the first-ever trial using hESCs-derived cells to treat spinal cord injury, announced that it was halting the trial for financial reasons. At the time, the treatment appeared safe, but the company had not seen evidence of improvement in the patients. Geron is still following the five patients it treated but has not yet published any results.