Biological Treatment of Bacterial Keratitis

细菌性角膜炎的生物治疗

• 批准号: 9409020
• 负责人: Curtis R Brandt
• 金额: $ 17.12万
• 依托单位: AMEBAGONE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9409020
• 关键词: Affect; Amoeba genus; Animal Experiments; Antibiotic Resistance; Antibiotics; Asses; Awareness; Bacteria; Bacterial Infections; Benign; Biocontrols; Biological Response Modifier Therapy; Biology; Blindness; Cells; Collection; Communicable Diseases; Consultations; Cornea; Corneal Injury; Country; Data; Dose; Eating; European Union; Eye; Eye Infections; Formulation; Gel; Genome; Grant; Habitats; Half-Life; Hour; IACUC; Immune response; In Vitro; Infection; Inflammation; Investigational New Drug Application; Keratitis; Knowledge; Lead; Left; Legal patent; Letters; Measures; Methods; Microbial Biofilms; Mus; North America; Ophthalmology; Organism; Pain; Pathogenicity; Pathology; Phagocytosis; Phase; Positioning Attribute; Predisposition; Pseudomonas aeruginosa; Recovery; Redness; Research; Resistance; Rights; Safety; Schedule; Services; Soil; Staphylococcus aureus; Streptococcus pneumoniae; Symptoms; Technology; Temperature; Testing; Therapeutic; Time; United States Food and Drug Administration; Universities; Validation; Visual Acuity; Wisconsin; Work; Wound Healing; antimicrobial; cell mediated immune response; design; follow-up; healing; in vitro testing; in vivo; killings; microorganism; novel; novel strategies; pathogen; pathogenic bacteria; phase 2 study; professor; prototype; research and development; residence; safety testing; success

Project Summary/Abstract Bacterial keratitis (BK) is an infection of the cornea that, if left untreated, can cause blindness. Staphylococcus aureus (Sa), Streptococcus pneumoniae (Sp), and Pseudomonas aeruginosa (Pa) are three major causes of BK in North America. Symptoms of BK include pain, redness, inflammation, and opacity of the affected cornea and loss of visual acuity (1). AmebaGone Inc., (AG) partnered with UW-Madison Department of Ophthalmology to develop a novel biocontrol method to treat BK. AG holds issued patents and has expert knowledge related to use of Dictyostelid cells (DC), a benign, soil- dwelling organism known to destroy pathogenic bacteria through the phagocytosis. Issued patents broadly cover the use of DC to eat biofilm-enmeshed and free-living (planktonic) bacteria (“Therapeutic Ameba and Uses Thereof”; USPTO granted patent 8,551,471 and follow up patent US 8,551,671). A patent covering countries of the European Union has been filed and the firm has licensed rights to more than 3,000 DC strains from 3 worldwide collections occupying diverse natural habitats. Benign DC diverged from aquatic amoeba, some of which are pathogenic, over 1 billion years ago. In Phase I work, AG identified 36 Dicty strains capable of efficiently killing (> 4 log10 reduction in bacterial titers) Sa at eye temperature. Of these strains, AG identified 4 DC strains that reproducibly germinated to high levels and developed a gel formulation that increased the maximum recovery time from 1 to 16 hours. Additionally, AG tested safety of these DC strains and found no increase in corneal pathology or discomfort compared to the vehicle control. In the Phase II project AG proposes to: 1) Expand the target of DC from singular action against Sa to additional causative agents of BK- Pa and Sp, 2). Develop effective formulation and assess DC stability therein. 3) Conduct in vivo safety and basic biology testing of DC treatment in the eye, and 4). Quantify efficacy of DC cocktails in treating murine cornea infected with Sa, Pa, or Sp in vivo. The data generated in these studies will position us to prepare an Investigational New Drug (IND) application for the Food and Drug Administration (FDA).

项目摘要/摘要 细菌性角膜炎（BK）是角膜的感染，如果未治疗，可能会引起失明。金黄色葡萄球菌（SA）， 肺炎链球菌（SP）和铜绿假单胞菌（PA）是北美BK的三个主要原因。 BK的症状包括疼痛，发红，炎症和影响角膜的不透明性和视力丧失（1）。 Amebagone Inc.，（AG）与UW-Madison Ophthalmology合作开发了一种新型的生物防治方法 治疗BK。 AG拥有已发行的专利，并具有与使用Dictyostelid细胞（DC）有关的专家知识，这是一种良性，土壤 - 已知通过吞噬作用破坏致病细菌的生物。发行的专利广泛涵盖了 DC可以吃生物膜含有的和自由生活（浮游生物）细菌（“治疗性ameba并使用”； uspto授予 专利8,551,471，并随访美国8,551,671）。欧盟的专利涵盖国家已被申请 该公司拥有从3个全球收藏中的3,000多个DC菌株的许可权，占据了潜水员的自然权利 栖息地。良性直流与水生变态性分歧，其中一些是致病性的，超过10亿年前。在第一阶段 工作，AG确定了36个dicty菌株，能够有效杀死（细菌滴度减少> 4 log10）SA。 温度。在这些菌株中，AG鉴定出4个DC菌株，这些菌株菌株又呈发芽至高水平并形成了凝胶 将最大恢复时间从1个小时增加到16小时的形成。此外，AG测试了这些DC的安全性 与车辆对照相比，菌株并发现角膜病理或不适感没有增加。在第二阶段项目中 AG提案：1）将DC的目标从针对SA的单数动作扩展到BK-PA的其他病因和 SP，2）。在其中开发有效的公式和评估DC稳定性。 3）进行体内安全性和基本生物学测试 眼睛中的直流处理，4）。量化直流鸡尾酒的效率，以治疗被SA，PA或SP感染的鼠角膜 体内。这些研究中产生的数据将使我们为研究性新药（IND）申请准备 食品和药物管理局（FDA）。