20 Years of CIRM: The evolution of a CIRM-funded therapy for macular degeneration

Written by guest contributor Amy Adams

In celebration of CIRM’s 20th anniversary, we are reflecting on some of the early projects we supported that have since advanced to clinical trials.

One such trial for a form of blindness originated with a 2007 SEED grant to David Hinton, MD, of the University of Southern California (USC) and later with a 2008 Disease Team Planning grant to Dr. Hinton’s long-time collaborator Mark Humayun, MD, PhD, also at USC. Dr. Humayun and Dr. Hinton collaborated with Dennis Clegg, PhD, of the University of California, Santa Barbara (UCSB), and together they received a Disease Team Award. Altogether, the group has received nearly $40 million for their work, leading to a stem cell therapy for blindness.

The team was focused on the most common form of blindness, age-related macular degeneration or AMD, which affects about 200 million people worldwide. With AMD, cells at the back of the eye called the retinal pigmented epithelium (RPE) break down and can no longer support cells of the retina, which detect light and allow us to see. Without the RPE cells, retinal cells degenerate, and people slowly lose their vision.

The team’s approach started with human embryonic stem cells (hESCs), which can mature into any cell type in the body. They planned to grow those stem cells into RPE cells, layer them on top of a synthetic membrane, and then implant the membrane behind the retina. The group plans to use the same RPE cells for each patient, which avoids the need to create entirely new batches of stem cells from each patient. A one-size-fits-all approach can treat more people and cost less.

In this 2011 interview with a woman living with macular degeneration, Dr. Humayun describes his team’s approach:

From the lab to patients

Dr. Humayun and his team later tested their approach in what’s called a Phase 1 clinical trial, funded by a Disease Team Therapy Development III award. This is the research stage, when scientists are simply testing to make sure an approach that worked in the lab is safe for humans. It involves a small number of people and isn’t intended to test whether the approach works. The idea is to make sure something is safe before giving it to more people. In this case, however, early results from the Phase 1 trial pointed towards potential benefits for patients, enough to persuade the researchers that it was worth moving to later-stage clinical trials.

This video, produced by USC in 2018, shows Dr. Humayun before he implanted cells in the very first patient. In it, he says, “No matter how much one prepares, the first patient is always something very special.”

Next Step: Expanding the trial 

Often, universities like USC can run small Phase 1 trials, but testing a potential therapy in more people generally requires the greater resources of a company. In this case, Dr. Humayun, Dr. Hinton, and Dr. Clegg founded a company in Portola Valley, California, called Regenerative Patch Technologies, which received $12 million in funding from CIRM in 2024 to run the Phase 2 trial. For this trial, the team developed a way of freezing the lab-grown RPE cells on a membrane so they can be distributed to where patients are located. Developing this manufacturing step was time-consuming, but it ensures that the trial can be open to people from all across California, and that any eventual therapy can benefit people far from where the cells are being stored.

Jane Lebkowski, PhD, President of Regenerative Patch Technologies, is no stranger to stem cell-based therapies. At both Geron and Asterias, she worked on hESC-based therapies for spinal cord injury. Now, at Regenerative Patch Technologies, Dr. Lebkowski said that she’s “bringing that experience to AMD.”

“The way that the therapeutic has evolved under CIRM funding exactly matches the development path that the agency hopes will bring transformative new disease treatments to Californians,” said Paul Webb, PhD, Senior Science Officer and Program Manager for Clinical Development. “Early academic studies have transitioned to clinical trial stage research. Further development is now in the hands of a nimble startup company, which is in a position to perform the studies needed to attract the funding that will be required for regulatory approval and to bring the treatment to the market.”

Since 2007, when CIRM first began funding this project, the agency has supported a total of 68 grants to study and treat various forms of vision loss, including other approaches to treating macular degeneration. It is unlikely any one approach will work for all people. With many potential therapies under development, we have the best chance of reaching the most people with an effective treatment.