UCLA researchers begin first stem cell trials to treat eye diseases

Researchers at the Jules Stein Eye Institute (JSEI) have begun two clinical trials to determine the safety of stem cell therapy and patients’ ability to tolerate it for the treatment of two common, currently untreatable degenerative eye diseases. This FDA-approved study is only the second in the United States to use human embryonic-derived stem cells in patients and the first to address eye diseases.

Twelve patients with the dry form of age-related macular degeneration (dry AMD) will be enrolled for one trial, and 12 with Stargardt’s macular dystrophy will be signed up for the other. While these patients still have some vision, all are legally blind. Currently, early participants are being screened by a battery of tests to ensure they don’t have other conditions, including cancer.

"There are substantial screening and health issues that have to be looked at before these patients undergo the surgery," said principal investigator Dr. Steven Schwartz, JSEI’s retinal division chief and Ahmanson Professor of Ophthalmology at the David Geffen School of Medicine and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "It’s major eye surgery in which we will be putting retinal pigment epithelial (RPE) cells derived from human embryonic stem cells into a special place in the eye, called the subretinal space. It’s our hope that the procedure and the therapy turn out to be safe and that we can continue to move forward to learn more about this new therapy."

Researchers are hoping that one day stem cell therapy will transform the way doctors treat diseases — by replacing diseased cells with stem cells that have the singular ability to turn into heart cells, eye cells or any other that might be needed. Schwartz made clear, however, that no one, including the patients, has any expectations of significant visual improvement, although preclinical studies showed that eyesight among test subjects did improve substantially.

"Patients understand that there may be little or no benefit to them directly in terms of this procedure," Schwartz said, adding that there are risks, known and unknown, associated with any new therapy. "But these patients are all excited to do it because they want to open the door for this emerging field. They are true pioneers. The patients are the real heroes here." The study, which began last April, is slated to be completed by September 2013.

Help can’t come too soon for those suffering from these eye diseases. The dry form of macular degeneration is the most common form of the disease and the leading cause of blindness in the developed world, especially among people over the age of 55. The number of people affected by this disease is expected to double over the next 20 years as the population ages. In contrast, Stargardt’s Macular Dystrophy can affect those at the other end of the age spectrum, usually starting in children between 10-20 years old.

In both cases, the layer of RPE cells located beneath the retina deteriorates and atrophies. Over time, the death of these cells and the eventual loss of photoreceptors, or light-sensitive cells, in the eye can lead to blindness as central vision is gradually destroyed.

Surgeons will inject 50,000-plus new RPE cells into the patient’s subretinal space, the space where native RPE cells are found and an "immunoprivileged" part of the eye where an immune system attack is less likely. These factors, natural immune privilege and pinpointing the anatomic location, theoretically improve the cells’ chances of implanting and functioning. "This is well-studied, and we are taking a conservative, biologically plausible first step that is hopefully optimized for success." Schwartz said.

The eye is also a good candidate for stem cell therapy because researchers will be readily able to see what the RPE cells are doing and measure whether the transplant has an effect on eye functions, Schwartz explained.

The results of Schwartz’s research could have a profound impact on the future of the therapy. "Key learnings from this study may potentially lay the foundation for clinical regenerative medicine in the eye for decades to come," he said.

The sponsor of the tests, Advanced Cell Technology Inc. (ACT) of Marlborough, Mass., has been working on developing the therapy for the last decade. JSEI’s Clinical Research Center, conceived by Institute Chairman Dr. Bartly Mondino and run by Dr. Gary Holland, will monitor the trials taking place at UCLA and at four or five other collaborating eye institutes. The Casey Eye Institute at the Oregon Health and Science University in Portland, Ore., is currently enrolling patients, and other collaborating partners will be named later.

"It’s because Jules Stein Eye Institute has the Clinical Research Center, thanks to the vision of Dr. Mondino, that’s allowing us to do this work," Schwartz said. "Another big factor is the research excellence of UCLA, which uniquely positions us to undertake these trials."

"We have great hopes for this," said Mondino, who added that no one can predict what will happen because this has never been tried before. "The Clinical Research Center has the infrastructure to support such a trial to optimize the possibility of success. We have the expertise of Dr. Schwartz and his team in the retinal division. We have the cells from ACT. I think we have the right combination here to ensure the best possible outcome."

Schwartz also applauded Dr. Owen Witte, head of UCLA’s regenerative medicine group, founding director of the UCLA Broad Stem Cell Research Center and the President's Chair of Developmental Immunology, and Dr. Donald Kohn, who runs UCLA’s GMP (good manufacturing practices) laboratory, for their assistance.

"They were both inspirational," Schwartz said. "Their leadership and advice have been invaluable."

The GMP laboratory is where the RPE cells created at ACT will go for final preparation before being given to patients, explained Kohn, whose own research involves using bone marrow stem cells in the treatment of certain blood diseases. "Since we have such a facility up and running, it allows UCLA to immediately move into this kind of pioneering trial," he said.

The trials’ high profile meant that the Clinical Research Center coordinated with not only the regenerative medicine company and the FDA, but with UCLA’s research infrastructure, including the Office of Research Administration, the Institutional Review Board as well as the Office of Contracts and Grants Administration.

"We were able to bring together vice chancellors and deans from the different programs, the University of California Office of the President, clinical administrators and coordinators in a productive, open, strategic and far-sighted way," Schwartz said. "Everything just clicked. And it worked just the way universities are ideally supposed to work.

"It’s an honor and a privilege to be doing this research and leading a team at a great university of this caliber. We just want to get it right, respect the patients and hopefully come up with key findings so that science and society can go forward," he said.