New offerings in leading-edge gene and cell therapy

Audrey Poppers has spent much of her life helping and offering hope to others, even as a sight-stealing diagnosis made it difficult to keep up many of her passions. Now Poppers is on the receiving end of a treatment through a clinical trial at the Byers Eye Institute at Stanford that has offered her hope for a better future.

Poppers is part of a clinical trial for one of two leading-edge therapies being deployed at the Byers Eye Institute to slow, halt, or possibly even improve vision in those who previously had no other treatment options. The trials, one using stem cell therapy to treat dry age-related macular degeneration (AMD) and another that uses gene therapy to treat retinitis pigmentosa, are testing breakthroughs that have been gaining traction in medicine for the past decade due to advances in biotechnology and genetics research.

“When I saw the potential of regenerative medicine and stem cells, I knew it was a great opportunity to try to help patients who are losing vision and have no treatments to help them,” said Theodore Leng, MD, FACS, professor of ophthalmology at the Byers Eye Institute who is working on both clinical trials, and leading the stem cell therapy trial at Stanford. 

Leng, who is also the director of clinical and translational research as well as ophthalmic diagnostics at the Byers Eye Institute, is working closely with Vinit Mahajan, MD, PhD, professor of ophthalmology, who is leading the gene therapy clinical trial at Stanford.

Both gene and stem cell therapies require surgery to deliver specific cells that are missing or beneficial in a targeted area of the eye. They both aim to halt vision loss and restore functional vision in people with degenerative diseases.

The pair have been buoyed by the early results of the trials, as participants report the treatments are working — sometimes even better than expected. 

Stem cell therapy

In stem cell therapy, the cells, which can take on many different forms based on the body’s needs, are injected into the eye to replace dead or damaged cells. The stem cells may even proliferate over time, creating more of the missing or damaged cells if needed.

Poppers is part of the stem cell therapy trial targeting those with dry AMD, a disease that affects a person’s central vision, making it hard or impossible to see directly ahead. She underwent a stem cell transplant in her right eye and returns regularly to the Byers Eye Institute for evaluation and care.

“I can see well enough to set the dial on the oven, the burglar alarm, and I can see my husband's face if I get close enough,” Poppers said. “I can't drive any longer, which is a great sadness for me, but that's all right; I can walk outside and be safe, which I don’t think would be the case without this treatment.”

Macular degeneration has changed Poppers’ life dramatically. The retired elementary school teacher-turned-administrator guided education for young people for most of her career. After retirement, she volunteered at a bird sanctuary — cats and dogs would pull at her heartstrings too much, she said. Then she drove for Meals on Wheels, delivering nutritious food in her community. Poppers loved all of it.

But each of those callings ended one by one as her macular degeneration worsened, making the tasks required for each role impossible.

“My right eye was deteriorating pretty rapidly and I was losing a lot of my vision,” Poppers said. “Since the stem cell placement, my right eye has improved a little bit and it has stabilized, so it hasn't progressed. I'm very grateful for that.”

Nearly 20 million Americans have AMD, according to recent data published in JAMA Ophthalmology. Those struggling with the disease have few options for treatment, and the options that exist currently only slow progression of the disease.

But Poppers and many of her fellow clinical trial participants have reported the treatment halted vision loss in the eye that received the stem cells. Multiple participants have said the treatment has even given them back a little of the vision they previously lost.

The clinical trial is the latest in more than a decade of stem cell research and clinical studies and trials on stem cell therapy for Leng. He even received a highly competitive grant from the California Institute for Regenerative Medicine (CIRM) to further his pre-clinical research and prepare for a separate clinical trial to treat AMD with stem cell therapy.

“The ultimate goal for our grant from CIRM is to go to another clinical trial and improve the lives of the 620,000 Californians out there that have this slowly progressive and debilitating blinding disease,” Leng said. “Of course, the work will also help AMD patients around the world to improve their everyday function and their ability to enjoy life.”

Gene therapy

Gene therapy involves packaging tailored genetic material into vectors, like a virus, but one that cannot make a person sick. Those vectors make their way into cells in the eye to alter how they fight disease or may even introduce a new gene that can effectively deactivate certain genetic disorders.

The gene therapy clinical trial is also showing promise to halt vision loss, and possibly even restore some vision to those with retinitis pigmentosa, the genetic degenerative eye disease that has recently received broad attention after being featured in the 2024 film Blink.

Retinitis pigmentosa is a group of rare genetic eye diseases that cause cells in the retina — the light-sensitive tissue in the back of the eye — to break down, leading to blindness, often before the age of 60. In the United States, an estimated 100,000 people suffer from the condition, but worldwide, more than 1.5 million people are affected, according to recent peer-reviewed studies on the condition.

Mahajan has worked on gene therapy research and clinical trials since its early days in ophthalmology, and the current clinical trial is the first gene therapy for the eye performed at Stanford. The Byers Eye Institute was poised to participate in the trial because of its faculty’s ability to conduct robust gene testing and patient identification, as well as advanced capabilities in imaging, surgery, and clinical trial design.

“What's really special at Stanford is that we have laboratories developing gene therapies, and under the same roof, we are testing gene therapies in clinical trials,” Mahajan said.

The newest trial is targeting X-linked retinitis pigmentosa, a severe form of the disease that affects about one in every 15,000 people. Men are most susceptible to the disease because they have only one X chromosome, so if that chromosome carries the diseased gene, it will affect them. Women have two X chromosomes, and as long as one of their X chromosomes is free of the diseased gene, they will not suffer from the disease. If either of their X chromosomes carry the disease, however, they will be carriers.

Gene therapy has great potential for diseases like X-linked retinitis pigmentosa because even one healthy copy of the gene delivered correctly to the eye can have a positive effect, correcting the disease and improving vision.

“This feels kind of like a miracle because this is a disease carried in genes that have been passed down for generations and all around the planet,” Mahajan said.

Next steps

Already Mahajan and Leng are planning additional clinical trials that will use the latest research and the findings from existing clinical trials to move safe and effective treatments forward for patients who lack options today.

“The original goal of the gene and stem cell therapy trials was really just to delay and slow down the disease, but very soon after surgery, our patients reported their vision was actually better,” Leng said.

For Poppers, who is in excellent health in every way except for her vision loss, those advances offer hope for a better future, both for herself and for others.

“I'm grateful for a chance to have improved my own vision, but I am also happy to be part of a study that I think is so important, because so many hundreds of thousands of people are affected,” she said. “I hope this will result in treatments that help other people.”