Open label safety and efficacy pilot to study mitigation of equine recurrent uveitis through topical suppressor of cytokine signaling-1 mimetic peptide

• Published in: Scientific reports Vol. 12; no. 1; pp. 7177 - 11
• Main Authors: Plummer, Caryn E., Polk, Timothy, Sharma, Jatin, Bae, Sanghyo Sarah, Barr, Olivia, Jones, Amari, Kitchen, Holly, Wilhelmy, Michelle, Devin, K., Clay Smith, W., Kolaczkowski, Bryan D., Larkin, Joseph
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/250/127; 631/250/24; 631/250/249; 631/250/251; 631/250/2520; 631/250/256; 631/250/38; 631/250/516; 692/699/3161; 692/699/3161/3177; Animals; Autoimmune Diseases; Bioinformatics; Blindness; Chronic Disease; Cytokines; Cytokines - metabolism; Horse Diseases - drug therapy; Horses; Humanities and Social Sciences; Inflammation; Janus kinase; Janus kinase 2; multidisciplinary; Patients; Peptides; Peptides - metabolism; Pilot Projects; Rodents; Science; Science (multidisciplinary); SOCS-1 protein; Suppressor of Cytokine Signaling 1 Protein - metabolism; Suppressor of Cytokine Signaling Proteins - metabolism; Uveitis; Uveitis - drug therapy; Uveitis - veterinary
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-11338-x

Equine recurrent uveitis (ERU) is a painful and debilitating autoimmune disease and represents the only spontaneous model of human recurrent uveitis (RU). Despite the efficacy of existing treatments, RU remains a leading cause of visual handicap in horses and humans. Cytokines, which utilize Janus kinase 2 (Jak2) for signaling, drive the inflammatory processes in ERU that promote blindness. Notably, suppressor of cytokine signaling 1 (SOCS1), which naturally limits the activation of Jak2 through binding interactions, is often deficient in autoimmune disease patients. Significantly, we previously showed that topical administration of a SOCS1 peptide mimic (SOCS1-KIR) mitigated induced rodent uveitis. In this pilot study, we test the potential to translate the therapeutic efficacy observed in experimental rodent uveitis to equine patient disease. Through bioinformatics and peptide binding assays we demonstrate putative binding of the SOCS1-KIR peptide to equine Jak2. We also show that topical, or intravitreal injection of SOCS1-KIR was well tolerated within the equine eye through physical and ophthalmic examinations. Finally, we show that topical SOCS1-KIR administration was associated with significant clinical ERU improvement. Together, these results provide a scientific rationale, and supporting experimental evidence for the therapeutic use of a SOCS1 mimetic peptide in RU.