By KOSAKU NARIOKA And PHRED DVORAK CONNECT | Wall Street Journal | 06/27/2013
TOKYO—Japan this week took a big step forward in the race to develop stem-cell therapies, giving preliminary approval for the first-ever human study of a treatment that reprograms the patient's own cells to regenerate damaged tissue.
A key panel of Japan's Health Ministry on Wednesday approved what would be the world's first clinical research for induced pluripotent stem cells, known as iPS cells, in a study that would focus on the cells' use in eye disease. That decision sets the stage for likely final approval by the health minister as early as next month, with the first human implants of the iPS cells potentially taking place next year, according to the ministry and government-backed Riken, the research institution whose Center for Developmental Biology is applying for permission to conduct the study.
If approved, the study could help put therapy using iPS technology—a relatively new process whereby mature cells are reprogrammed to develop, like embryonic cells, into other kinds of tissue—on a fast track for development. To speed things along, Riken is seeking permission not for a clinical trial—which is harder to win approval for and typically takes 10 years to conduct—but a type of pretrial clinical research allowed under Japanese regulations. Such clinical research can be very small scale—Riken is only aiming to try the treatment out on a handful of patients—and can't lead immediately to approved therapies or commercialization.
Yet it would still be a speedy start for trying out a stem-cell therapy on people: iPS cells were first produced in 2006, and there are still many unknowns and concerns about the process—in particular that the transformed cells will keep on multiplying, producing cancerous growths in patients. Even treatments using embryonic stem cells, which have been cultured and studied for decades, are still in very early clinical trials.
"Clearly there are some safety issues that should be dealt [with] regarding the production of the iPS cells and the risk of tumor formation,'' says Nissim Benvenisty, director of the stem-cell unit at the Hebrew University of Jerusalem. "But I'm sure investigators will try to deal with these issues in the best way.''
In the U.S., some patients are already getting new retina cells to treat macular degeneration derived from embryonic stem cells. There was a successful safety test of such stem-cell treatment with patients last year at the Jules Stein Eye Institute in Los Angeles, using cells developed by Advanced Cell Technology Inc. ACTC -1.28% in Marlborough, Mass.
Japan has a special fondness for iPS, which was pioneered by a Japanese scientist, Kyoto University's Shinya Yamanaka, and for which Mr. Yamanaka won a Nobel Prize last year. Japan's Education Ministry said it's planning to spend 110 billion yen ($1.13 billion) on iPS research during the next 10 years. In April, Japanese parliament even passed a law calling for Japan to make regenerative medical treatments like iPS technology available for its citizens "ahead of the rest of the world.'' The parliament also plans later in the year to discuss bills that would speed the approval process and ensure the safety of such treatments.
"Even now, there are lots of people who think that you can't go [to clinical testing] with iPS yet,'' says Masayuki Yamato, an expert on regenerative medicine at Tokyo Women's Medical University. "But [the panel] has given the OK, so Japan is a pretty amazing country in that regard…It's betting on iPS.''
The proposed iPS study would focus on people suffering from a form of age-related macular degeneration, a disease of the eye where the retina degenerates, causing loss of vision. The research team would reprogram patients' skin cells to become iPS cells, which would be induced to develop into retinal cells. The retinal cells would then be implanted in the patients' eyes.
The study will concentrate on making sure the treatment doesn't cause serious safety risks for patients. The initial group of patients will be those for whom existing medical treatment has failed, a Riken spokesman said. If those tests go well, the institute hopes to conduct another round of tests to see if the transplants can help restore eyesight—with an ultimate goal of developing a treatment that can be commercialized.
One eventual obstacle, even if tests go well, could be cost: Mr. Yamato says initial estimates for the treatment run around ¥50 million ($512,000) per person.
Before getting final approval for the study to proceed, Riken's application is scheduled to be evaluated by one more Health Ministry group in mid-July, said ministry official Akinori Hara. That group has never yet overturned an approval granted by the initial panel, he added. The minister generally gives a final go-ahead a week or two later, he said.
The research team will start preparing for implants as soon as the ministry authorizes the study, said Riken spokeswoman Natsuko Izumi. The team is aiming to perform the first human implant as early as the next fiscal year, beginning April 2014, she said.