Ten years ago, a biotech startup called Advanced Cell Technology (ACT) began trying to create retinal cells from human embryonic stem cells. Because this newly discovered type of cell could both replenish itself and differentiate into any cell type in the body, it was seen as an ideal source of replacement tissue. This year, after spending $20 million on its quest, the company will begin its first human tests of the treatment. ACT won approval from the U.S. Food and Drug Administration this week to start clinical trials of an experimental treatment for age-related macular degeneration, the most common cause of blindness in people older than 60.
It is only the third clinical trial of an embryonic-stem-cell-based therapy to be approved by the FDA. ACT won permission to test the same therapy in patients with a rare genetic disorder related to macular degeneration last fall, and a second company, Geron, began testing a cell therapy for spinal-cord injury last year. However, because macular degeneration is so common—roughly 17 million Americans suffer from the disease—ACT’s new therapy has the biggest potential impact on patient health. No treatments are now available for the so-called dry form of macular degeneration, which accounts for 90 percent of cases.
“If you can intervene early and preserve vision, that’s a major accomplishment,” says Raymond Lund, a researcher at the Casey Eye Institute at Oregon Health Sciences University, who directed some of the animal studies of the therapy.
ACT’s treatment replaces a type of retinal cell called retinal pigment epithelium, which begins to deteriorate early in the course of the disease. These cells help support the photoreceptors that translate light signals from the environment into electrical signals for the brain to process. Without healthy retinal pigment epithelium, the photoreceptors begin to sicken and die, causing loss of vision.
To create the cells, researchers at ACT grow large vats of embryonic stem cells and then differentiate them into retinal pigment epithelium, a process that takes about four to five months. The cells are then injected into the eye. Tests in rodents with similar retinal degeneration show that the cells can slow deterioration and improve vision. “The cells wind up in the back of the eye, as they should, and are able to sustain vision,” says Lund.
The clinical trial of 12 patients will initially assess whether it is safe to inject the cells, but clinicians will also test such things as the patients’ visual acuity and their eyes’ electrical function, the retinal equivalent of an EKG.
“I am really excited; [ACT] is pioneering the use of embryonic stem cells in ocular disease, and that’s a great thing,” says Thomas Reh, director of Neurobiology and Behavior at the University of Washington. Reh is not involved in the research and is not affiliated with ACT.
Both ACT and Geron have faced huge hurdles in getting approval to begin human tests. Because their therapies are the first to be tested in the U.S., the FDA has required extensive safety testing to show that the cells won’t behave in unwanted ways once implanted. For example, undifferentiated stem cells, which have yet to develop into a specific type of tissue, can form a type of tumor called a teratoma when injected into mice. But Robert Lanza, ACT’s chief scientific officer, emphasizes that the therapy uses only differentiated cells. And the company has done extensive testing to show that it has eliminated undifferentiated cells from its final product.
Lanza adds that the eye is the ideal place to test embryonic-stem-cell-based therapies. “We are using a small number of cells that are going into a localized area of the eye,” he says. “Unlike any other site in the body, you can look into the eye in real time to see if anything funky is going on.”
A number of questions remain to be answered, including how well the cells will survive in a diseased eye. Increasing evidence suggests that macular degeneration is in part an immune defect, and some people with the disease have signs of inflammation in the retina, which may it more difficult for the implanted cells to take root. “That’s something animal models haven’t been able to look at carefully,” says Reh.
It’s also not yet clear whether, if the cells do survive, they will delay or prevent further vision loss, or actually improve vision. Transplants of retinal pigment epithelium cannot replace lost photoreceptors, but they may help damaged photoreceptors function better and in turn enhance vision.