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.
专长：重症烧伤救治。广东省医学会烧伤科分会主任委员、广东省医疗行业协会伤口管理分会副主委。
擅长：烧伤后期整形、各种顽固性创面如各种压力性溃疡、糖尿病足等治疗、危重烧伤救治、烧伤内脏并发症的防治、各种外伤后疤痕畸形的修复重建。发表论文40余篇。
擅长大面积深度烧伤的早期救治、各种烧烫伤创面的综合处理、烧伤后瘢痕增生挛缩畸形的修复。长期致力于急性皮肤缺损、慢性皮肤溃疡（褥疮、糖尿病足等）的外科治疗。
擅长领域：介入微创诊疗血管性疾病等，如下肢动脉硬化闭塞症、糖尿病足、血管畸形、静脉曲张、动静脉血栓形成、静脉狭窄闭塞等。
东莞康华医院国际造口治疗师，采用全球倡导的伤口湿性愈合疗法和造口专科护理新技术，在糖尿病溃疡足、下肢动/静脉溃疡、骨髓炎、外科术后感染/脂肪液化、肿瘤伤口、放射性皮炎、痛风破溃感染、压力性损伤（压疮）、液体外渗、造口并发症、失禁、瘘管等方面提供专业化的诊治、咨询及健康教育。
从事骨科临床工作和外科学教学工作30年。擅长骨关节疾病、四肢骨折和手外伤的保守治疗、手术治疗（关节置换手术、四肢骨折内固定手术、创伤修复手术）；各类创面的修复：包括糖尿病足、难治性痛风破溃感染伤口、创伤术后伤口不愈合。
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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