Systemic Treatment with a KLK5 Inhibitor Shows Efficacy in a Murine Model of Netherton Syndrome

Systemic treatment with DS77754007, a specific KLK5 inhibitor, demonstrated significant efficacy in improving skin manifestations in a mouse model of Netherton Syndrome (NS). The study involved C57BL6 mice with a homozygous mutation in the Spink5 gene, treated with DS77754007 or various antibodies over 4 weeks. Results showed that the three item severity (TIS) score was significantly lower in mice treated with DS77754007 compared to those treated with vehicle or anti-IL-4/13R, anti-TNFa antibodies. Although anti-IL-17A antibody also reduced the TIS score, DS77754007 was more effective, suggesting that systemic KLK5 inhibition could be a promising treatment for NS.