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.

项目概要 寻常痤疮是一种皮肤炎症，影响 80% 的年轻人，并且经常诱发 即使经过适当的治疗，痤疮也是由痤疮丙酸杆菌在激素环境下引起的。 青春期伴随的变化和皮脂诱导的主要治疗方法是根除。 C. 痤疮和减少炎症 然而，治疗时间较长（通常持续 4-8 周）并且有效果。 近年来与两种一线抗生素耐药性的出现有关。 克林霉素和红霉素目前占 30-50%，这种严峻的形势凸显了对药物的需求未得到满足。 这一第一阶段 STTR 提案是通过合作伙伴关系提出的。 George Liu 实验室和 Pulsethera Inc 旨在扩大这些初步发现并设计治疗原型 多重耐药性痤疮感染的 PI Ji-Xin Cheng（博士）是生物光子学专家 George。 刘（医学博士）是细菌中包括过氧化氢酶在内的发色团研究的先驱，也是第一个发现 Liu 和 Cheng 正在合作开发金黄色葡萄球菌中葡萄球菌黄素的抗氧化特性。 新型抗菌光疗法（科学进展，2020，7：1903117）。 加州大学圣地亚哥分校的 George Liu 实验室和波士顿大学的 Ji-Xin Cheng 实验室发现过氧化氢酶自然表达在 广谱细菌（革兰氏阴性和革兰氏阳性）和真菌物种，可以通过 蓝光 LED 和更有效的脉冲蓝光（准备中的手稿），我们已经观察到。 过氧化氢酶的光灭活有效地使包括痤疮丙酸杆菌在内的病原体对极低浓度敏感 该团队的中心假设是过氧化氢酶的光失活能够使 C. 痤疮病原体对产生 ROS 的免疫细胞和抗菌剂的影响 为了检验这一假设，我们首先将 开发过氧化氢酶光灭活原型并验证其协同杀死痤疮丙酸杆菌的效率 然后我们将确定过氧化氢酶光灭活与过氧化氢的功效（目标 1）。 过氧化物在动物模型体内治疗痤疮（目标 2）。 我们期望加速消除促炎性痤疮丙酸杆菌将改善结果 并避免需要长期服用抗生素，因为长期服用抗生素会导致抗生素耐药性。