Dry age-related macular degeneration treatment may help prolong eye health

Bothell, WA-The "dry" form of age-related macular degeneration (AMD) affects 90% of the 29 million people worldwide with AMD. Although the dry form can progress to "wet" and lead to central vision loss, little can be done to save patients' vision.

Ryo Kubota, MD, PhD, and a team of researchers at Acucela Inc. are working to develop orally delivered visual cycle modulation therapies that selectively target cells within the retina to protect visual acuity. By modulating the visual cycle, they believe they can protect the retina from light damage, improve retinal vasculature, and reduce the accumulation of toxic by-products, including A2E (pyridinium bis-retinoid).

Dr. Kubota explained that the research centers on the idea that we don't fully utilize our eyes' rods, which are responsible for our night vision, but little else. They collect information and feed it to our brain, which does not fully process it. This activity causes the rods to slowly deteriorate as we age, and as the rods cease to support cone cells, vision suffers. The deterioration causes a build-up of toxic by-products (lipofuscin) associated with the pathological mechanisms that lead to dry AMD and other degenerative retinal diseases, including Stargardt's disease.

"We are modulating rods, which are responsible for generating 90% of toxic by-products in the eye to prevent progression of AMD," said Dr. Kubota, Acucela's chairman, president and chief executive officer.

The visual cycle modulators under development by Dr. Kubota's team slows the visual cycle, thereby protecting rod cells from deterioration, allowing the rods to support cone cells longer, and reducing the build-up of lipofuscin.

It all would happen via a daily pill, which is easier and more convenient than the injections currently proving effective at treating the wet form of AMD.

"We think this is changing the paradigm in how ocular diseases are treated," he said.

Early trials show a "significant decrease in the incidence of conversion to wet AMD" when administered doses of the Acucela product in development, which the company is calling ACU-4429, Dr. Kubota said. "We show in pre-clinical models we can get rid of neovascularization. It's huge."

Dr. Kubota discovered the glaucoma gene, myocilin, while performing ocular research at Keio University, Tokyo, in 1997. He continued his research at the University of Washington, Bothell, and later joined the faculty as an assistant professor. His work today on ACU-4429 is building on the visual cycle modulation he helped to pioneer more than 10 years ago. However, the work needed the backing of large, multi-disciplinary team to come up with a drug as a safe and potent molecule, and he licensed his findings from the university and founded Acucela in 2002.