“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.