Xiaolong A. Zhou1 | Michael B. Burns2 | Ziyou Ren1 | Elise Stagaman2 | Stefan J. Green3 | Lok Yiu Ashley Wu3 | Lynna Yang1 | Stephanie Rangel1 | Lydia Rabbaa1 | Amy S. Paller1
1Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA | 2Department of Biology, Loyola University Chicago, Chicago, Illinois, USA | 3Genomics and Microbiome Core Facility, Rush University Medical Center, Chicago, Illinois, USA
Correspondence: Amy S. Paller (该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。)
Received: 6 February 2025 | Revised: 6 June 2025 | Accepted: 3 August 2025
Funding: This work was supported by Applied Pharma Research.
Keywords: acid-oxidising solution | epidermolysis bullosa | hypochlorous acid | microbiome | Staphylococcus aureus | wounds
ABSTRACT
Epidermolysis bullosa (EB) is a group of rare genetic skin disorders characterised by skin fragility and chronic, painful wounds that are highly susceptible to bacterial infection, particularly by Staphylococcus aureus (SA). This study evaluated the efficacy of an acid-oxidising solution containing hypochlorous acid (HOCl) in reducing SA colonisation, promoting wound healing, and restoring a healthier microbiome in EB wounds. In a 12-week open-label pilot study, 15EB patients applied the HOCl-based spray (APR-TD011) daily to chronic wounds for 8weeks, with full-length 16S rRNA sequencing of wound swabs performed before, during, and after treatment. At baseline, 87% of patients were culture-positive for SA, and sequencing revealed that SA had the highest relative abundance (34%), followed by Acinetobacter guillouiae and Pseudomonas poae. SA relative abundance decreased precipitously by Weeks 4 (to 11%) and 8 (primary endpoint; to 10%, p<0.01), and this effect persisted at 4weeks post-treatment (Week 12; to 9.7%), including for methicillin-resistant SA. Concurrently, bacterial diversity increased, and wound sizes dimin ished in correlation with reduced SA levels (r=0.64). Younger patients exhibited greater SA reduction trends. The treatment was well-tolerated, with minimal adverse effects and high patient satisfaction. This study underscores the role of microbial dysbiosis in EB wounds and highlights HOCl-based solutions as a promising therapy to mitigate pathogenic burden and enhance wound.
Thomas H. Leung,1,2 Lillian F. Zhang,1 Jing Wang,1 Shoucheng Ning,3 Susan J. Knox,3 and Seung K. Kim1,4,5
1Department of Developmental Biology, 2Department of Dermatology, 3Department of Radiation Oncology, 4Howard Hughes Medical Institute, and 5Department of Medicine, Oncology Division, Stanford University School of Medicine, Stanford, California, USA.
Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB–dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB–driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB–dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB–mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.
伤口世界平台生态圈，以“关爱人间所有伤口患者”为愿景，连接、整合和拓展线上和线下的管理慢性伤口的资源，倡导远程、就近和居家管理慢性伤口，解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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