Mitigation of Equine Recurrent Uveitis through topical Suppressor of Cytokine signaling-1 (SOCS1) mimetic peptide: Open Label Safety and Efficacy Pilot study

Abstract

Abstract Recurrent Uveitis (RU), is a relapsing/remitting disease that accounts for more than 10% of severe visual handicaps in US patients per year, despite treatments that often include steroids. Even when effective, prolonged steroid use is accompanied by significant negative side effects. As such, there is a critical need for the development of novel therapeutic strategies to treat RU. Notably, equine recurrent uveitis (ERU) is the only spontaneous model of human recurrent uveitis, and is also a leading cause of equine blindness. RU is driven by aberrant inflammation from the immune system. Notably, the body naturally generates a family of intracellular proteins, known as suppressors of cytokine signaling (SOCS), which prevent excessive inflammatory responses. We have previously shown that topical application of an eye drop, containing a cell-penetrating peptide that mimics SOCS1 (SOCS1-KIR), could mitigate experimental uveitis in mice. In order to evaluate the ability to translate our preclinical findings we conducted a first in equine, open label study in which we evaluated the safety and efficacy of topical SOCS1 peptide administration in ERU patients. We found that topical SOCS1-KIR administration was well tolerated in equine patients. Moreover, topical administration of SOCS1-KIR peptide twice a day was associated with reductions in ocular discomfort, hyperemia, and aqueous flare. Additionally, biochemical analyses of SOCS1-KIR revealed an enrichment strategy that could potentially be utilized to optimize ocular peptide dosing. Together, these results prove justification for conducting larger additional treatment studies in horses, and exploring SOCS1-KIR use in humans.