Contrary to popular perception, retinitis pigmentosa (RP) is not a disease caused by a single genetic defect; it is a condition caused by many different genetic defects. The common thread is that each of the genetic defects kill “rod” photoreceptors in the retina — which make up 95 percent of the retina’s light sensitive cells — leaving the other 5 percent, the “cones,” virtually untouched.
Thanks to those remaining cones, patients with RP are able to see early in the disease but have reduced vision at night and in low-light settings. However, over time, cones gradually die, resulting in constriction of the visual field and causing tunnel vision and eventual blindness. A major contributor to cone damage and death is oxidative stress. There is no cure and not a single drug on the market offering hope, but Peter Campochiaro, M.D., Wilmer’s George S. and Dolores D. Eccles Professor of Ophthalmology and Neuroscience, is about to change that.
In 2021, he will begin a phase III trial of a drug he has been investigating for years, known as N acetylcysteine — NAC for short — that reduces oxidative stress and thereby provides some protection for cones. A phase III trial is the penultimate stage of drug approval. If this stage is successful, Campochiaro and colleagues will have delivered the first drug treatment for retinitis pigmentosa.
He called the phase II trial Fight RP. Phase III has been dubbed NAC Attack.
“In an initial clinical trial, NAC caused some short-term improvement in cone function. The next trial will determine if long-term treatment can prevent cones from dying and prevent progressive loss of visual field. That research will require four years of testing, so there’s work ahead,” Campochiaro says. NAC is already approved by the U.S. Food and Drug Administration (FDA) for treating another condition, which accelerates the approval process, as the drug is already shown to be safe, he notes.
RP is a genetic disease that gets handed down generation to generation, like some perverse lottery. So far, science has identified more than 50 genes involved in the various forms of retinitis pigmentosa. For scientists intent on developing effective gene therapies, it is necessary to pick those genes off one by one — a long, laborious process. NAC has the potential to help all RP patients, regardless of their specific genetic mutations.
While the eyes’ cones are initially spared in RP, Campochiaro explains, they gradually degenerate, resulting in progressive shrinking of the field of vision. With nine-tenths of its light-sensitive rod cells dead, the retina no longer utilizes as much oxygen, resulting in excessively high oxygen in the retina. All that excess oxygen produces toxic byproducts that attack the cones, causing critical components to oxidize. The damage builds up over time until the cone is no longer able to function and dies.
“The cones die in a particular pattern, starting with the cones in the periphery of the retina and progressing toward the center, resulting in constriction of peripheral vision until it is like looking through a tunnel,” he says. The hope is that NAC will preserve the cones and prevent the visual field from shrinking.
Over the years, Campochiaro’s NAC research has been propelled by the faithful support of philanthropists.
“In the earliest days of new research, the support of donors is critical. The National Institutes of Health [NIH] only wants to fund projects it has a strong idea will work,” Campochiaro says. “Philanthropy is the only way early studies can get off the ground.”
Marc Sumerlin knows this paradigm well. He’s been supporting Campochiaro’s research since his daughter was diagnosed with RP five years ago. Sumerlin views Campochiaro as a leader in RP on the global stage. For Sumerlin, the most promising aspect of the NAC study is the fact that NAC is already FDA-approved and therefore deemed safe to use. Too often, he’s seen a promising drug trial start only to be swallowed in the fundraising “Valley of Death,” where initial research is promising but not advanced enough to get NIH or big grants, and the project dies.
“Peter has a gift for the simple solutions,” Sumerlin explains of his high hopes for NAC. “I’m excited for my daughter because the science is proceeding faster than our best-case scenario. We’re grateful to have Peter on our side.” Another donor is Jonathan Wallace. It was a combined gift from him, his wife, and his brother and sister-in-law that got the NAC study started several years ago. To Wallace, the pace of the research has been inspiring. “To have a drug in phase III this fast is incredible. The decisions Peter made and the groundwork he laid back then have led to a significant result in a very short time,” Wallace says. “It’s just thrilling to be a part of it.”