Eliminating Acne Through Photo-Inactivation Catalase

通过光灭活过氧化氢酶消除痤疮

• 批准号: 10256426
• 负责人: George Y Liu
• 金额: $ 25万
• 依托单位: PULSETHERA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256426
• 关键词: Acne; Acne Vulgaris; Adolescence; Affect; Animal Model; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Antifungal Agents; Antimicrobial Effect; Antioxidants; Area; Asia; Bacteria; Benzoyl Peroxide; Biophotonics; Boston; Businesses; Candida auris; Capital; Cells; Clindamycin; Clinical; Collaborations; Communicable Diseases; Complex; Coupled; Development; Diabetes Mellitus; Doctor of Philosophy; Electronics; Enzymes; Erythromycin; Exposure to; Funding; General Hospitals; Generations; Gold; Gram-Negative Bacteria; Head; Hormonal Change; Hospital Departments; Human; Hydrogen Peroxide; Immune; Immunity; Immunocompromised Host; Infection; Inflammation; Inflammatory; Intellectual Property; Investments; Laboratories; Lasers; Light; Low-Level Laser Therapy; Manuscripts; Massachusetts; Medical; Medicine; Modeling; Multi-Drug Resistance; Mus; Pathogenicity; Pathway interactions; Patient Care; Peroxides; Phase; Phototherapy; Physiologic pulse; Privatization; Property; Reactive Oxygen Species; Resistance; Science; Sebum; Services; Skin; Small Business Technology Transfer Research; Staphylococcus aureus; Sunlight; Superoxide Dismutase; Superoxides; Testing; Therapeutic; Transplantation; Treatment Protocols; Universities; Water; Work; Yeasts; absorption; antimicrobial; antimicrobial drug; base; catalase; chromophore; chronic infection; comparative efficacy; design; drug resistant pathogen; effective therapy; emerging antibiotic resistance; expectation; experience; fungus; heme a; improved outcome; in vivo; medical schools; multi-drug resistant pathogen; novel; novel therapeutic intervention; pathogen; photonics; professor; prototype; staphyloxanthin; synergism; ultraviolet; wound; young adult

PROJECT SUMMARY Acne vulgaris is a skin inflammatory condition affecting 80% of young adults and can frequently induce permanent disfigurement even with appropriate treatment. Acne is caused by C. acnes in the setting of hormonal changes and sebum induction that accompany adolescence. The mainstay of therapeutics consist of eradicating C. acnes and reducing inflammation. However, treatment is prolonged (usually 4-8 weeks in duration) and has been associated in recent years with the emergence of antibiotic resistance. Resistance to two first line antibiotics clindamycin and erythromycin currently stands at 30-50%. This severe situation highlights an unmet need for novel and more effective treatment options. This phase I STTR proposal, through a partnership between the George Liu lab and Pulsethera Inc, aims to amplify these initial findings and to design a prototype for treatment of multi-drug resistant acne infections. The PI Ji-Xin Cheng (PhD) is an expert of Biophotonics. The co-PI George Liu (MD PhD) is a pioneer in the study of chromophores including catalase in bacteria and was the first to uncover staphyloxanthin’s anti-oxidant property in S. aureus. Liu and Cheng have an ongoing collaboration in developing novel antimicrobial phototherapies (Science Advances, 2020, 7:1903117). A recent collaboration between George Liu lab at UCSD and Ji-Xin Cheng lab at Boston University found that catalase, naturally expressed in a broad spectrum of bacterial (both gram-negative and gram-positive) and fungal species, can be inactivated by a blue light LED and more effectively by pulsed blue light (manuscript in prep). Consequently, we have observed that photo-inactivation of catalase effectively sensitizes pathogens including C. acne to very low concentration of hydrogen peroxide. The team’s central hypothesis is that photo-inactivation of catalase is able to sensitize C. acne pathogens to ROS-producing immune cells and antimicrobial agents. To test this hypothesis, we will first develop a catalase photo-inactivation prototype and validate its efficiency in killing C. acne in synergy with hydrogen peroxide (aim 1). We will then determine the efficacy of catalase photo-inactivation coupled with peroxide in the treatment of acne in vivo in an animal model (aim 2). By accomplishing the proposed studies, it is our expectation that accelerated elimination of the pro-inflammatory C. acnes will lead to improved outcome and obviate the need for long courses of antibiotics that are the cause of antibiotic resistance.

项目摘要 痤疮伏gar是一种皮肤炎症状况，影响80％的年轻人，并且经常诱发 即使经过适当的治疗，永久毁容也是如此。痤疮是由痤疮在荷尔蒙的环境中引起的 适应青少年的变化和皮脂诱导。理论的支柱包括根除 C.痤疮并减少炎症。但是，治疗延长（通常为4-8周），并且具有 近年来与抗生素耐药性的出现有关。对两条第一线抗生素的抗性 克林霉素和红霉素目前为30-50％。这种严重的情况强调了对 新颖，更有效的治疗选择。这一阶段我通过 George Liu Lab and Pulsethera Inc，旨在扩大这些初始发现并设计用于治疗的原型 多药抗性痤疮感染。 Pi Ji-XI-Xin Cheng（博士学位）是生物探测器的专家。乔治的副驾驶 刘（MD PhD）是细菌中包括过氧化氢酶在内的发色团研究的先驱，并且是第一个发现的人 金黄色葡萄球菌葡萄糖黄质的抗氧化特性。刘和郑在开发方面有一个持续的合作 新型抗菌光疗（Science Advances，2020，7：1903117）。最近的合作 UCSD的George Liu Lab和波士顿大学的Ji-Xin Cheng Lab发现，Catalase自然而然地在 广泛的细菌（革兰氏阴性和革兰氏阳性）和真菌种类可能被A灭活 蓝光引导，并通过脉冲蓝光更有效（准备中的手稿）。因此，我们观察到 过氧化氢酶的照片灭活有效地感觉到病原体，包括痤疮浓度很低 过氧化氢。该团队的中心假设是过氧化氢酶的照片灭活能够感知C。 痤疮病原体对产生ROS的免疫细胞和抗菌剂。为了检验这一假设，我们将首先 开发过氧化氢酶的照片传动原型，并验证其在杀死C.痤疮协同作用的效率 过氧化氢（AIM 1）。然后，我们将确定过氧化氢酶摄影的效率 在动物模型中，过氧化物在体内治疗痤疮（AIM 2）。通过完成拟议的研究， 我们期望加速消除促炎的痤疮痤疮将导致结果改善 并消除对抗生素耐药性的长期抗生素的需求。