CIRM funds many projects seeking to better understand diseases of blindness and to translate those discoveries into new therapies.
Over a million Americans are legally blind, with another 3.2 million suffering significant visual impairment1. While there are several causes of blindness, the leading cause of all visual impairment is age-related macular degeneration, which affects 1.7 million Americans.
California’s stem cell agency funds research into potential therapies for three of the causes of blindness. All the research teams are seeking to use various forms of stem cells to rescue or replace cells in the eye damaged or threatened by the diseases. Several groups are working on ways to restore vision for people with age-related macular degeneration (AMD). Other projects are looking to preserve vision in patients with retinitis pigmentosa (RP), and to restore clarity to the surface of eyes impacted by corneal disease.
AMD affects 8 million Americans and accounts for over 50% of vision loss cases in white Americans. In AMD, the layer of cells that support the photoreceptors is destroyed. Without this support system, the photoreceptors, the cells that actually allow us to sense light start to malfunction. CIRM-funded teams are looking at various methods of replacing this layer of support cells called RPE (retinal pigment epithelial) cells. Some are using embryonic stem cells as a starting point to generate new RPE cells. Others are using stem cells obtained by reprogramming adult cells to be like embryonic cells, which could potentially come from the patients’ themselves.
Retinitis pigmentosa (RP) is an inherited and progressive vision loss disease that has an incidence of 1:4000 and leaves most patients legally blind by mid-life. RP destroys the light-sensing photoreceptors in the retina. CIRM-funded researchers are seeking to use stem cells to rescue these photoreceptors from further damage and potentially replace them with new ones.
Limbal Stem Cell Deficiency
The cornea, the outer surface of the eye, is constantly refreshed by stem cells that reside in neighboring tissue. But some people just don’t have enough of these stem cells, called limbal stem cells, to make enough new cornea cells. CIRM-funded researchers are trying to correct this condition, limbal stem cell deficiency, by retrieving the few existing limbal stem cells, and using various techniques to expand them in the laboratory until there are enough cells to rebuild a healthy cornea.
Clinical Stage Programs
University of Southern California
This team is using embryonic stem cells to produce the support cells, or RPE cells, needed to replace those lost in AMD. Because these cells exist in a thin sheet in the back of the eye, they are assembling these sheets in the lab by growing the RPE cells on synthetic scaffolds. These sheets are then surgically implanted into the eye. They are testing the human embryonic stem cell-derived RPE cells in a Phase 1/2a clinical trial to treat the advanced dry form of AMD.
This team, led by Sophie Deng, is taking the patient's owns limbal stem cells and expanding their number in the laboratory, then returning them to the patient in the hope they will repair the damage caused by the disease and help restore vision or at least halt the progression of the disease. They are testing this in a Phase 1 clinical trial. They are also using novel diagnostic methods to assess the severity of the disease and the patient's response to treatment.
For retinitis pigmentosa, the team is using donor tissue to isolate cells that are part way down the path from neural stem cells to adult eye tissue. These retinal progenitor cells are grown in large quantities in the lab and then injected into the eye. The team suggests the cells could help in two ways. They may be able to protect the photoreceptors not yet damaged by the disease, and they may be able to form new photoreceptors to replace those already lost. The team tested the safety of transplanting human retinal progenitor cells into patients with RP in a phase 1/2 clinical trial that is now completed. CIRM is now funding a Phase 2 trial, sponsored by a jCyte, that is testing this treatment in a larger group of RP patients (see trial below).
The same team from UC Irvine is now conducting a Phase 2b clinical trial for retinitis pigmentosa using the same stem cell derived retinal progenitor cell therapy. The trial, which is sponsored by the company jCyte, will test the treatment in a larger patient population to determine whether the treatment is effective at restoring some vision. After finishing patient enrollment, the team will conduct patient follow up studies and collect of all clinical outcome measures.