Selection of a lead candidate for the development of a novel anti-inflammatory therapeutic

选择开发新型抗炎疗法的主要候选者

• 批准号: 10156864
• 负责人: Aleah Fox Caulin
• 金额: $ 29.97万
• 依托单位: PEEL THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10156864
• 关键词: Acute; Anti-Inflammatory Agents; Biological; Biological Assay; Biology; Biotechnology; Blood Vessels; Blood specimen; Caymans; Cell Count; Cessation of life; Chemotaxis; Chromatin; Clinical Trials Design; DNA; Data; Deposition; Development; Diabetes Mellitus; Disease; Drug Kinetics; Ensure; Enzyme Inhibition; Enzyme-Linked Immunosorbent Assay; Event; Fluorescence; Half-Life; Heart; Heart Diseases; High Pressure Liquid Chromatography; Histones; Hour; Human; Immune; Immune response; In Vitro; Infection; Inflammation; Inflammatory; Injections; Laboratories; Lead; Legal patent; Licensing; Measures; Methionine; Microbe; Modality; Modeling; Molecular; Morbidity - disease rate; Mus; Nature; Neonatal; Nervous System Trauma; Norleucine; Pathogenesis; Pathway interactions; Pattern; Peptides; Peritonitis; Phagocytosis; Pharmacodynamics; Phase; Plasma; Positioning Attribute; Prevention; Property; Protein-arginine deiminase; Proteins; Rivers; Sepsis; Small Business Innovation Research Grant; Stroke; Therapeutic; Therapeutic Agents; Tissues; Treatment Factor; Universities; Utah; Work; antimicrobial; base; cecal ligation puncture; chronic inflammatory disease; commercialization; comparative; comparative efficacy; coronavirus disease; drug development; experience; experimental study; extracellular; factor A; human disease; improved; in vitro activity; in vivo; inhibitor/antagonist; intravenous injection; lead candidate; live cell imaging; mortality; mouse model; neutrophil; novel; novel strategies; novel therapeutic intervention; peptide A; peptide drug; pharmacokinetics and pharmacodynamics; polymicrobial sepsis; pre-clinical; preclinical study; preservation; prevent; screening; stroke model; success; therapeutic development; vascular injury

PROJECT SUMMARY/ABSTRACT PEEL Therapeutics, Inc. (PEEL) is pioneering a novel approach to prevent morbidity and mortality associated with inflammatory disease through the inhibition of neutrophil extracellular traps (NETs). NETs are lattices of decondensed chromatin decorated with histones and antimicrobial proteins extruded by polymorphonuclear leukocytes (PMNs) to trap and kill microbes. While regulated NET formation contains infection, dysregulated NET formation leads to inflammatory tissue damage and vascular injury. NETs have been implicated in human diseases characterized by inflammation, including sepsis, stroke, diabetes, and heart disease. The ability of NET- inhibitory factors (NIFs) to block PMN-dependent NET formation makes this newly described class of endogenous peptides a promising therapeutic modality for diseases caused and/or exacerbated by NET-dependent inflammatory events. In this Phase I SBIR, PEEL will quantify and compare the biological activity and pharmacokinetics of two NIFs in vitro and in vivo. The lead NIF peptide will move forward in the development of a novel anti-NET therapeutic. After completing these SBIR Phase I tasks, PEEL Therapeutics will be in an excellent position to advance its new and patented NIF-based therapeutic to further preclinical studies. These efforts by PEEL Therapeutics hold the potential to disrupt and improve the treatment approach to both acute and chronic inflammatory diseases.

项目总结/文摘