Researchers report a recombinant biologic derived from blood-feeding ticks may be a potential treatment for allergic eye disease
Researchers led by Malihe Eskandarpour, MSc, from Ocular Immunology Group, University College London Institute of Ophthalmology, London, reported that nomacopan (Akari Therapeutics), a recombinant biologic derived from blood-feeding ticks, may be a potential treatment for allergic eye disease due to its ability to down-regulate the LTB4/C5 pathways in experimental allergy conjunctivitis (EAC).1
The drug is a second-generation complement inhibitor with dual activities, i.e., it acts on complement component C5 and prevents release of C5a and formation of C5b-9 as well as inhibits leukotriene B4 (LTB4) activity, both of which are part of the immune/inflammatory response.
Nomacopan seems to have the potential to fill a gap in the treatment of sight-threatening vernal keratoconjunctivitis in children, which generally is treated with steroids.
Investigating the inflammatory cascade
The investigators conducted a study to determine how LTB4 and complement C5 contribute to an EAC model. They explained that EAC is a model of allergic eye disease that is primarily driven by effector Th2 cells and mast cells.
During EAC, conjunctival inflammation is detectable by 5 days and shows elevated levels of conjunctival interleukin (IL)-9-expressing CD4+T cells and mast cells in tissues and cells expanded from conjunctival explants.
The investigators observed significantly increased levels of tryptase+ conjunctival mast cells that co-expressed intracellular IL-9 in the subepithelial area within the fornix of the conjunctival EAC tissues.
In mice with EAC treated with topical nomacopan, the disease was suppressed significantly and there was a decrease in IL-9-expressing CD4+T cells. Two studies2,3 reported previously that Th9 and Th2 cells produce IL-9.
“Topical nomacopan attenuated conjunctivitis in EAC and decreased IL-9 in CD4+T cells. We concluded that IL-9 was up-regulated during vernal keratoconjunctivitis and EAC. Nomacopan significantly suppressed EAC severity, accompanied by a decrease in IL-9-producing Th2 cells, Th2 cells, and to a lesser extent, Th9 cells, suggesting a key pro-inflammatory role for IL-9-secreting CD4+T cells in allergic eye disease. Our findings support nomacopan as a potential treatment for allergic eye disease due to its ability to down-regulate LTB4/C5 pathways in EAC,” Dr. Eskandarpor and colleagues concluded.