Designed Antimicrobial Peptides for Treatment of Infectious Acne Vulgaris

设计用于治疗传染性寻常痤疮的抗菌肽

• 批准号: 9464005
• 负责人: Kathryn W Woodburn
• 金额: $ 22.42万
• 依托单位: RIPTIDE BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9464005
• 关键词: Accounting; Acne; Acne Vulgaris; Adolescent and Young Adult; Advanced Development; Affect; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial susceptibility; Bacteria; Biological Assay; Biological Sciences; Cells; Chemicals; Chemistry; Clindamycin; Cutaneous; Data; Dermatologic; Dermatology; Development; Disease; Drug resistance; Engineering; Environment; Evaluation; Exhibits; Extracellular Matrix; Failure; Funding; Goals; Grant; Human; In Vitro; Infection; Inflammatory; Invaded; Investigation; Kinetics; Lead; Luciferases; Mediating; Microbial Biofilms; Modeling; Nature; Organism; Patients; Peptides; Phase; Physicians; Predisposition; Property; Propionibacterium acnes; Reporter Genes; Resistance; Sebum; Site; Skin; Small Business Innovation Research Grant; Socialization; Solid; Therapeutic Index; Time; Toxic effect; United States; Visit; analog; antimicrobial; antimicrobial drug; antimicrobial peptide; bacterial resistance; bactericide; base; burden of illness; chronic inflammatory skin; cost; cytotoxicity; design; healing; in vivo; innovation; keratinocyte; killings; microorganism; mouse model; novel; novel therapeutics; pathogen; permissiveness; phase 2 study; preclinical study; psychologic; public health relevance; restoration; self esteem; skin disorder; targeted agent; theories

Public Abstract. Acne vulgaris is a chronic inflammatory skin disorder affecting more than 80% of all adolescents and young adults worldwide. Acne causes a substantial cutaneous and psychologic disease burden, often creating crippling effects in patients’ self‑esteem and socialization. Acne management results in high monetary and physician use demands in the United States, accounting for more than 5 million doctor visits each year and resulting in costs in excess of $2.5 billion. Antibiotic therapy has been integral to acne management however the widespread, and often permissive, use of antibiotics has led to the emergence of resistant P. acnes bacteria. Moreover, biofilm formation by P. acnes, which comprise sophisticated colonies of microorganisms encased in a resilient dense extracellular matrix increases its resistance against antimicrobial agents. Biofilms are. Despite the critical need for new antibiotics with novel modes of action, the development of antibacterial agents has drastically declined in recent years. Designed antimicrobial peptides (dAMPs), created by Riptide Bioscience Inc, are chemically derived from naturally occurring AMPs which are ubiquitous in nature and provide the first line of defense against invading pathogens. dAMPs have a reduced likelihood of spurring bacterial resistance, exhibit potent antimicrobial activity against the Gram-positive P. acnes pathogen and have known anti-inflammatory properties. Based on the initial encouraging antimicrobial results observed in planktonic isolates and biofilm cultures for P. acnes and demonstrated in vivo antibacterial and anti-inflammatory activity, we propose that these novel peptides may treat acne infections while exhibiting less susceptibility to bacterial resistance. In this proposed investigation, the in vitro antibacterial activity of dAMPs against P. acnes isolates and biofilm will be evaluated, dAMP-mediated P. acnes bactericidal kinetics in the absence and presence of sebum will be assessed, the cytotoxicity of dAMPs on human keratinocytes will be determined and the antimicrobial efficacy of the lead peptides in ameliorating infection in an inflammatory P. acnes murine model will be determined. If successful, a product candidate will be selected to be advanced, via a SBIR grant-funded Phase II study, to FDA-required preclinical studies with the goal of developing a commercially viable therapy for the treatment of infectious acne vulgaris.

公共摘要。 寻常痤疮是一种慢性炎症性皮肤病，影响 80% 以上的青少年和年轻人 痤疮给世界各地的成年人带来巨大的皮肤和心理疾病负担，常常造成瘫痪。 对患者自尊和社会化的影响 痤疮管理导致金钱和医生的高使用。 美国每年有超过 500 万人次就诊并产生费用 超过 25 亿美元的抗生素治疗已成为痤疮治疗中不可或缺的一部分，但其应用广泛且广泛。 抗生素的使用往往会导致耐药性痤疮丙酸杆菌的出现。 由痤疮丙酸杆菌形成，它由复杂的微生物菌落组成，包裹在有弹性的致密结构中 尽管迫切需要，但细胞外基质增加了其对抗菌药物的抵抗力。 对于具有新颖作用方式的新型抗生素，抗菌药物的开发急剧下降 近年来，Riptide Bioscience Inc 设计的抗菌肽 (dAMP) 是通过化学方法制成的。 源自天然存在的 AMP，它们在自然界中普遍存在，并提供针对 入侵的病原体激发细菌耐药性的可能性降低，表现出有效的作用。 对革兰氏阳性痤疮丙酸杆菌病原体具有抗菌活性，并具有已知的抗炎特性。 基于在浮游菌株和生物膜培养物中观察到的令人鼓舞的初步抗菌结果。 痤疮并表现出体内抗菌和抗炎活性，我们建议这些小说 肽可以治疗痤疮感染，同时表现出对细菌耐药性的敏感性较低。 调查，将评估 dAMP 对痤疮丙酸杆菌分离株和生物膜的体外抗菌活性， 将评估在不存在和存在皮脂的情况下 dAMP 介导的痤疮丙酸杆菌杀菌动力学， 将确定 dAMP 对人角质形成细胞的细胞毒性以及先导物的抗菌功效 如果成功，将确定肽在炎症性痤疮丙酸杆菌小鼠模型中改善感染的作用。 产品候选者将通过 SBIR 拨款资助的 II 期研究被选为推进至 FDA 要求的产品 临床前研究，旨在开发一种商业上可行的治疗感染性痤疮的疗法 寻常的。

项目成果

Designed Antimicrobial Peptides for Topical Treatment of Antibiotic Resistant Acne Vulgaris.

设计用于局部治疗抗生素耐药寻常痤疮的抗菌肽。

• 发表时间: 2020-01-13
• 作者: Woodburn, Kathryn W;Jaynes, Jesse;Clemens, L Edward
• 通讯作者: Clemens, L Edward