Endolysin Significantly Improves Symptoms With Atopic dermatitis: bridging the gap from research to clinical practice

Ling Kui^1*Jinqun Huang^2,3Guoyun Wang¹Jiamin Zhao^2,3Shuangshuang Wang¹Xiaoxing Qing^2,3Leifeng Liu⁴Jinafei Hu⁴Lianjia Chen⁵Xingchun Wang⁵Qing Li⁶Yuqian Zhao^2,3Yuanyue Tang^2,3Ke-Xu Xiong¹Shuxia Zhan¹Honghua Ding¹Junling Wang¹Hua Cai¹Qing Zhang¹Xiaoyan Zi¹Qiong Deng⁷Lian Gao⁷Xuan Wang⁶Chaowei Zou⁸Huilin Yang⁹Yue Xiao¹⁰Bin Yang⁶Bingfeng Leng^11,2Li Zhang¹Gang Hu¹

• ¹Dermatology Department & Medical Cosmetology Department, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong 518067, China, Shenzhen, China
• ²Shenzhen Beichen Biotech Co., Ltd., Shenzhen, Guangdong 518000, China, Shenzhen, China
• ³Hong Kong Rising Biotechnology Co., Ltd., Hong Kong 999077, China, Hong Kong, China
• ⁴Suzhou ReadCrystal Biotechnology Co., Ltd, Suzhou, Jiangsu 215000, China, Suzhou, China
• ⁵01 Life Institute, Shenzhen, Guangdong 518000, China, Shenzhen, China
• ⁶Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510000, China, Guangzhou, China
• ⁷The People's Hospital of Longhua Shenzhen, Shenzhen, China
• ⁸Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510000, China, Guangzhou, China
• ⁹Peking University Shenzhen Hospital, Shenzhen, China
• ¹⁰Department of Dermatology and Venereology, West China Hospital, Sichuan University, Chengdu, Sichuan 610000, China, Chengdu, China
• ¹¹Functional Microbiology R&D Center, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, P.R China, Shenzhen, China

Atopic Dermatitis (AD), a chronic inflammatory skin disease characterized by pruritus, dryness, redness, oedema, scratching, and lichenification, ranks as the leading cause of non-fatal skin disease burden globally. Current therapeutic strategies for AD primarily act by inhibiting inflammatory pathways, yet largely fail to address Staphylococcus aureus (S. aureus) control unless exudative lesions are present. However, concerns over treatment-related adverse effects, long-term safety profiles, and emerging drug resistance underscore the remaining substantial unmet clinical needs in this field. Background/Objectives: To evaluate the safety and efficacy of endolysin gel in treating AD. Methods: An infection-driven dermatitis model with AD-like features was established. Following treatment with Staphyrase® or in other control groups, skin disease severity scores, S. aureus CFU, and key inflammatory cytokines were assessed. An open-label, single-center, investigator-initiated clinical study (ChiCTR25001192) was conducted in which participants, who received the endolysin gel twice daily, underwent follow-up assessments at baseline, treatment weeks 1 and 2, with an optional extension up to 3 months. Results: Statistically significant reductions in skin lesion scores, S. aureus load, and AD-related immune mediators (i.e., IgE, TSLP, IL-33) were observed in the Staphyrase® group relative to the model group. All 20 enrolled adult subjects completed the clinical study, with no tolerability issues reported, indicating a favorable safety profile of the endolysin gel. Compared to baseline, EASI, SCORAD, IGA, VAS, and DLQI scores demonstrated significant decreases at both Day 7 and Day 14 (all P < 0.05). Notably, Participant No. 11, who underwent extended follow-up until Week 8, exhibited substantial improvements in redness, lichenification, severe scratching, oozing, and dryness. The Endolysin gel showed consistent safety and efficacy in improving both acute and chronic AD lesions. Conclusions: Topical endolysin gel is a well-tolerated, effective, and promising agent for the treatment and proactive maintenance of mild-to-moderate AD in adults.