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 寻常痤疮是一种影响80%的年轻人的皮肤炎性疾病， 即使经过适当的治疗也会造成永久性的毁容。痤疮是由C.青春痘在激素的设置 变化和皮脂诱导伴随青春期。主要的治疗方法包括根除 C.痤疮和减少炎症。然而，治疗是长期的（通常持续4-8周）， 近年来与抗生素耐药性的出现有关。对两种一线抗生素的耐药性 克林霉素和红霉素目前占30- 50%。这一严峻局势突出表明， 新的和更有效的治疗选择。第一阶段STTR提案通过与 乔治刘实验室和Pulsethera公司，旨在扩大这些初步发现，并设计一个原型的治疗 多药耐药痤疮感染。皮继新（PhD）是生物光子学专家。合作伙伴乔治 刘（医学博士）是研究发色团的先驱，包括细菌中的过氧化氢酶， 葡萄黄素在S.金黄色。刘和程在开发方面正在进行合作 新的抗微生物光疗（Science Advances，2020，7：1903117）。最近的合作， 加州大学圣地亚哥分校的乔治刘实验室和波士顿大学的程继新实验室发现，过氧化氢酶，自然表达在一个 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（手稿准备）。因此，我们观察到， 过氧化氢酶的光失活有效地使包括C.痤疮浓度非常低 过氧化氢该团队的中心假设是过氧化氢酶的光失活能够使C。 痤疮病原体对产生活性氧的免疫细胞和抗菌剂的影响。为了验证这一假设，我们将首先 开发了过氧化氢酶光灭活原型，并验证了其对C.痤疮协同作用 过氧化氢（目标1）。然后，我们将确定过氧化氢酶光灭活与 过氧化物在动物模型体内治疗痤疮中的应用（目的2）。通过完成拟议的研究， 是我们的期望，加速消除促炎性C。痤疮将导致改善的结果 并强调需要长期使用抗生素，这是抗生素耐药性的原因。