As we grow older, a common disease called macular degeneration can threaten our eyesight. An experimental stem cell treatment proved effective at halting this disease with no serious side effects up to a year later, a study published in the New England Journal of Medicine found. It is the first treatment using personalized, genetically identical cells derived from the patient.
The macula is the spot in the center of your eye’s retina. When that tissue begins to thin and break down, this is referred to as macular degeneration, a blurring of the sharp central vision necessary for driving, reading and other close-up work. Most people develop this disease as they age.
For the new study, researchers in the laboratory for retinal regeneration at RIKEN Center for Developmental Biology in Japan tested an experimental stem cell treatment on a 77-year-old woman diagnosed with “wet,” or neovascular age-related, macular degeneration.
The “wet” form of the disease involves blood vessels positioned underneath the pigment epithelium (a layer of retinal cells) growing through the epithelium and harming the eye’s photoreceptor cells. In Japan, wet age-related macular degeneration is the most common form, but in Caucasian populations, only about 10% of people with age-related macular degeneration gets that form.
The “dry” form involves the macula breaking down without growth of blood vessels where they’re not supposed to be.
To stop the progress of wet macular degeneration, the researchers performed surgery to transplant a sheet of retinal pigment epithelial cells under the retina in one of the patient’s eye.
The transplanted cells had been derived from autologous induced pluripotent stem cells, which are reprogrammed cells. They were created using cells from the connective tissue of the woman’s skin.
One year after surgery, the transplanted sheet remained intact, and there was no evidence of lasting adverse effects. Although the patient showed no evidence of improved eyesight, her vision had stabilized.
An eye on stem cells
Michael P. Yaffe, vice president of scientific programs at the New York Stem Cell Foundation Research Institute, said the study was “incredibly thorough, careful and well-documented.”
“Many experts in the field of regenerative medicine believe that the treatment of macular degeneration and other retinal diseases will be among the first areas of success in the use of stem cell-derived tissues,” said Yaffe, whose foundation was not involved in the RIKEN study.
Yaffe said this optimism stems from preliminary studies using retinal cells derived from stem cells in animals. Scientists are also hopeful because the procedures to generate pure cells of the correct type and surgical techniques necessary for transplantation have already been developed.
“A number of research groups are moving toward developing stem cell-based treatments for age-related macular degeneration and other retinal diseases,” Yaffe said.
One, the London Project to Cure Blindness, has an ongoing clinical trial for a stem cell treatment. And an unrelated 2012 UCLA study showed that human embryonic stem cells restored the sight of several patients who had become nearly blind due to macular degeneration.
The National Eye Institute at the National Institutes of Health is planning a similar study using patient-specific pluripotent stem cells, according to Kapil Bharti, a Stadtman Investigator in the Unit on Ocular Stem Cell & Translational Research at the institute. After getting approval to conduct a phase I safety trial, the institute will treat 10 to 12 patients to check safety and tolerability of stem cell-based eye tissue transplants.
“Data from 10 to 12 patients is needed to show that the implanted cells are indeed safe,” he said, adding that the trial is likely to begin in 2018.
“While researchers have used embryonic stem cell derived cells to treat age-related macular degeneration, (the RIKEN study) is the first study that used induced pluripotent stem cells,” said Bharti, who was not involved in the research.
Both induced pluripotent stem cells and embryonic stem cells can be used to make other kinds of cells of the body, explained Bharti. However, induced pluripotent stem cells can be derived from adult skin or blood cells, rather than from embryos.
“Another big scientific advantage with induced pluripotent stem cells is that they can be made patient-specific (because it’s the patient’s own cells), reducing the chances of tissue rejection,” he said.
P. Michael Iuvone, a professor of ophthalmology and director of vision research at Emory University School of Medicine, also noted the importance of using the patient’s own stem cells.
Past studies have used embryonic stem cells to treat age-related macular degeneration, but there were problems related to rejection, when the body refuses to accept a transplant or graft, explained Iuvone, who was not involved in the latest study. In the new RIKEN study, the researchers took the patient’s own cells and converted them into retinal cells to avoid these complications.
“The results from the standpoint of the graft taking and surviving without any signs of any kind of toxicity or tumorigenicity are very positive,” Iuvone said. “But the weakness is, they only had one patient, and it’s very difficult to make any conclusions from one patient.”
He noted that the RIKEN researchers planned to work with more patients, but in 2014, the Japanese government passed a law that said regenerative medicine clinical trials could be performed only at medical institutions, not at research institutions such as RIKEN.
‘Major milestone’
Though the experiment was performed on a woman with wet age-related macular degeneration, it also might be useful for “dry” age-related macular degeneration, which is more common in the United States, according to Iuvone.
Currently, there are some effective treatments for age-related macular degeneration.
“The standard of care in most cases is to give injections of drugs that inhibit the growth hormones that is called vascular epithelial growth factor, or VEGF,” Iuvone said. “For most people, it at least slows the progression and in some cases actually improves visual acuity.”
Laser treatments have also been used but are on the decrease because of side effects. “Given the fact that the VEGF treatments seem to be effective, I think that most clinicians have turned to that,” Iuvone said.
Bharti believes the RIKEN study is a major milestone in the field. “We and others are learning from the Japan study,” he said.
Susan L. Solomon, CEO of the New York Stem Cell Foundation Research Institute, agrees.
“This study represents a fundamental advance in regenerative medicine, in the use of stem cell-derived tissues and in the treatment of eye disease,” she said. However, additional work and many more studies are needed, she said, before a safe and efficacious stem cell-based treatment will be available “to the broad and growing population with retinal disease” — all of us, growing older.