A pepidomimetic inhibitor of the receptor for C5aR (JPE1375) blocks the mechanism that draws inflammatory cells into the disease process of age-related macular degeneration (AMD). When blocked, the numbers of neutrophils and macrophages decrease substantially, and in turn, choroidal neovascularization (CNV) also decreases, according to Anthony Adamis, MD, Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago.

The inhibitor is a small molecule of only 40 µm in diameter. The formulation is stable in biologic fluids, under high temperatures, and with various solvents. The molecule is released slowly, which lowers the patient treatment burden.

The rationale for this treatment approach is to block the complement cascade, which raises a question over the target point in the cascade, he said. Dr. Adamis and his group chose to block inflammation associated with complement activation, which has been seen as a component of drusen and CNV.

"The complement cascade is part of the immune system in the eye that manages infection," he said. "By selective blockage, the numbers of neutrophils and macrophages that can infiltrate are reduced and the CNV can be reduced by about 50%."

Sustained release of this complement inhibitor, besides reducing the treatment burden, also should reduce the peak concentration in the eye and serum and lengthen the duration of drug exposure, which may be beneficial in a chronic disease such as AMD.