Embryonic Stem Cells Improve Vision, Appear Safe at 22 Months

Veronica Hackethal, MD

October 15, 2014

More than half of the patients treated for age-related macular degeneration (AMD) with embryonic stem cells had improved vision after a median of 22 months follow-up, according to a study published online October 15 in the Lancet. Moreover, investigators found no evidence of abnormal cell proliferation, rejection, or other serious ocular or systemic events linked to the transplants.

The results of the phase 1/2 studies, conducted in the United States, provide the first long-term safety data for human embryonic stem cells (hESCs) and the first data showing biological activity in any type of human disease.

The study paves the way for further developments in this field. Embryonic stem cells have been studied in animals for more than 3 decades, but until now, there have been no reports about their long-term safety and effectiveness in humans.

"Since hESCs are among the most versatile stem cells that exist, these results have significance for the entire pluripotent stem cell field," lead author Robert Lanza, MD, from Advanced Cell Technology in Marlborough, Massachusetts, told Medscape Medical News. "Cell reprogramming technologies are in development that will hopefully eliminate the risk of rejection and allow cell therapies to expand beyond immunoprivileged sites such as the eye."

The eye is a good place to start, however, because it can more readily tolerate foreign cells without triggering an immune response, which means there may be less risk for transplant rejection in the eye.

Some patients reported "dramatic improvements" in their lives after treatment, Dr Lanza continued.

"Overall, the vision of patients improved about three lines on the standard visual acuity chart; whereas the untreated fellow eyes did not show similar improvements in visual acuity," Dr Lanza explained. "The patients also reported notable improvements in their general and peripheral vision, as well as in near and distance activities."

He added, "Little things, which we all take for granted, have made a huge difference in the quality of their life. We treated a 75-year-old horse rancher who lives in Kansas. He was blind in the eye we treated. One month after treatment, his vision had improved 10 lines, and he can even ride his horses again." Others were able to use computers again or to read their watches.

Eighteen Patients, Two Diseases

The researchers conducted two prospective phase 1/2 studies that enrolled participants between July 2011 and January 2014. They transplanted hESC-derived retinal pigment epithelium into the subretinal space in nine participants with Stargardt's macular dystrophy and in nine participants with atrophic age-related macular degeneration. Taken together, these diseases are among the leading causes of blindness in adults and children in developed countries. No proven treatments exist.

Participants received 50,000, 100,000, or 150,000 cells in one eye; the other eye remained untreated. The patients also received oral immunosuppression. Researchers followed participants for a median of 22 months, and two patients were followed for more than 36 months.

Some of the challenges with hESCs involve their potential to form tumors and the risk for transplant rejection. Adverse events that occurred in this study, such as cataract formation and infection, were thought to be related to surgery and immunosuppression, rather than the hESC cells. No participants experienced teratoma formation or graft rejection.

Best-corrected visual acuity increased in 10 of 18 eyes and stayed about the same or improved in seven eyes. The visual acuity of eight of the 18 eyes increased by at least 15 letters during the first year. The vision in untreated eyes failed to improve in a similar manner. One participant with Stargard's macular dystrophy had a decrease of more than 10 letters.

"In terms of a phase 1 study, it met all the milestones that they wanted to reach. This study really does lay the groundwork for future studies. It's an accomplishment for the field," Anthony Atala, MD, Director of the Wake Forest Institute for Regenerative Medicine at Wake Forest University School of Medicine in Winston-Salem, North Carolina, told Medscape Medical News. Dr Atala authored an editorial linked to the study.

The results could potentially apply to induced pluripotent stem cells (iPCs). IPCs come from the skin and have the potential to revert back to embryonal stem cells, Dr Atala explained. Because iPCs come from the patient, rather than from embryos, their use may not be so laden with the ethical issues sometimes involved in the use of embryonal stem cells. Researchers in Japan recently announced the very first use of iPCs in a human patient with macular degeneration, Dr Atala mentioned.

Next steps would be to determine the best dose and to confirm these results in larger numbers of patients. Other challenges include figuring out how to manufacture these cells for human use and how to use them safely and efficiently, according to Dr Atala.

"When you're talking about stem cell therapy, there are a lot of questions on how these things should be done. Having this trial behind us shows that a lot of these challenges can in fact be overcome," Dr Atala emphasized, "This is definitely a step in the right direction."

Phase 2 clinical trials for this study are expected to begin by the end of the year.

The study was supported by Advanced Cell Technology. Dr Lanza and four coauthors are employees of Advanced Cell Technology. One or more of the authors reports receiving research support, honoraria, or consultancy fees from one or more of the following: Alcon, Bausch and Lomb, Allergan, Genentech, Regeneron, Avalanche, Mid Atlantic Retina, Arctic, Acucela, Alimera, Opthotech, Salutaris, Thrombogenics, Biogen, ReNeuron, and Advanced Cell Technology. Dr Ata has disclosed no relevant financial relationships.

Lancet. Published online October 15, 2014. Abstract

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