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).

项目总结/文摘