Drug Delivery with Nanoparticles Slows Macular Degeneration

February 20, 2015

Using nanoparticles to provide sustained delivery of the drug retinylamine, researchers at Case Western Reserve University slowed disease progression in a mouse model of macular degeneration. The emerging treatment worked by preventing the accumulation of vision-robbing, toxic waste products in the retina, which is the hallmark of age-related macular degeneration (AMD) and Stargardt disease, the most common form of juvenile macular degeneration. Results of the research were published in the journal Biomaterials. The scientists are conducting additional lab studies to determine if the therapy can be moved into clinical trials.

Zheng-Rong Lu, Ph.D., the study’s lead investigator, says that the most important advancement in the study was using nanoparticles — manmade particles that are 1/100th the diameter of a human hair — to get the treatment to the back of the eye.

“The key innovation of our work was to use nanoparticles to control the release of the drug at a relatively low therapeutic concentration over a prolonged period,” he explains. “The approach can improve efficacy and, at the same time, minimize potential toxic side effects, because only the retina is targeted.”

Made of a biodegradable plastic and approved for human use, the nanoparticles in the Case Western research effort were loaded with retinylamine. Once delivered, they provided continuous release of the drug as they degraded over seven days. The researchers are working to increase the length of time the drug is released to make it better suited for use in humans.

In previous lab research, Krzysztof Palczewski, Ph.D., a world-class pharmacologist and a collaborator on the study, discovered that retinylamine slowed the build-up of harmful vitamin A byproducts in macular degeneration.

Acucela, a Seattle-based biotechnology company, is conducting a 480-participant, Phase 2b/3 clinical trial of an oral drug similar to retinylamine for people with the advanced form of dry AMD known as geographic atrophy. The two-year human study is expected to conclude in July 2016. The company will report results for safety and changes in vision then.

Vitamin A is an essential component of the visual cycle, the complex biochemical process in the retina that makes vision possible. In people with healthy retinas, the accumulation of toxic byproducts that result from the process is minimal. But in those with dry AMD, toxin-containing deposits known as drusen develop underneath the retina. In Stargardt disease, deposits called lipofuscin, which also have toxic byproducts from the visual cycle, develop in a supportive layer of cells known as the retinal pigmented epithelium (RPE). In both conditions, the harmful substances lead to loss of RPE and, ultimately, photoreceptor cells and central vision.

“Delivering treatments to the back of the eye remains a challenge for many developers of retinal- disease therapies, so this advancement in nanoparticles is good news for our constituents,” says Stephen Rose, Ph.D., chief research officer, at the Foundation Fighting Blindness. “Also, retinylamine is a good drug candidate, as it’s showed promise for slowing macular degeneration. We look forward to hearing more about the progress of this research effort as it moves forward.”