A Novel Glycosaminoglycan-Based Therapeutic for Chronic Rhinosinusitis

一种基于糖胺聚糖的慢性鼻鼻窦炎治疗方法

• 批准号: 10323966
• 负责人: Abigail Pulsipher
• 金额: $ 100万
• 依托单位: GLYCOMIRA, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323966
• 关键词: Adrenal Cortex Hormones; Adverse effects; Affect; Air; Animals; Anti-Inflammatory Agents; Barium; Benzalkonium Chloride; Biological; Biological Assay; Blood specimen; Canis familiaris; Cardiovascular system; Cells; Clinical Trials; Complex; Data; Disease; Dose; Drug Costs; Drug or chemical Tissue Distribution; Emerging Technologies; Engineering; Ensure; Epithelial Cells; Etiology; Exhibits; Formulation; Genetic Transcription; Glycosaminoglycans; Goals; Guidelines; Health Expenditures; Heparin; Human; Immune; Impaired cognition; Impairment; Infiltration; Inflammation; Inflammation Mediators; Inflammatory; Injectable; Innate Immune Response; Intranasal Administration; Investigational Drugs; Investigational New Drug Application; Irrigation; Laboratories; Lead; Leukocytes; Measures; Mediating; Medical; Mental Depression; Methods; Micronucleus Tests; Modeling; Molecular Weight; Monoclonal Antibodies; Mucociliary Clearance; Mucolytics; Mucous body substance; Nasal Polyps; Natural Immunity; Nose; Operative Surgical Procedures; Outcome; Paranasal Sinus Diseases; Pathogenesis; Patient-Focused Outcomes; Patients; Pattern recognition receptor; Peptide Hydrolases; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Population; Prevalence; Production; Productivity; Property; Quality of life; Rattus; Recovery; Regulation; Reporting; Rivers; Route; Running; Safety; Saline; Sampling; Signal Transduction; Sinus; Sinusitis; Sleep Disorders; Sprague-Dawley Rats; Sputum; Steroids; Sulfate; Symptoms; TLR2 gene; Technology; Telemetry; Temperature; Testing; Therapeutic; Time; Tissues; Topical application; Toxicokinetics; Toxicology; Treatment Cost; analytical method; aqueous; base; chronic rhinosinusitis; clinical development; cost; cytokine; disorder control; drug candidate; drug distribution; effective therapy; experience; flexibility; improved; in vivo; lead candidate; light scattering; method development; neurobehavior; novel; novel therapeutics; pre-clinical; respiratory; safety study; seal; stability testing; therapeutically effective

PROJECT SUMMARY Chronic rhinosinusitis (CRS) is one of the most prevalent inflammatory diseases in the U.S., affecting up to 12% of the population and substantially diminishing the quality of life and productivity of patients. In four years, the annual U.S. health care expenditure to treat patients with CRS increased from $9B to $64B, with a corresponding rise in surgical treatment for those 20% of patients who fail medical management with the first line of defense – saline nasal irrigation and corticosteroid nasal sprays. Recently approved or emerging technologies for CRS continue to rely on corticosteroid treatment with new delivery methods. However, safety concerns over the long-term use of corticosteroids still remain, and the end result continues to be inadequate control of the disease. GlycoMira Therapeutics’ GM-1111 is a synthetic glycosaminoglycan-based drug candidate that targets innate immunity molecules Toll-like receptor 2 and 4 to reduce downstream inflammatory consequences, such as the production of inflammatory cytokines and influx of inflammatory immune cells into damaged tissues. In models of CRS, intra-nasal administration of GM-1111 outcompetes corticosteroids as an effective treatment for reducing sinonasal inflammation, with significantly decreased inflammatory cytokine production, leukocyte infiltration, mucus accumulation, and air-sinonasal epithelial cell barrier breakdown/impaired mucociliary clearance. Studies have additionally demonstrated that GM-1111 is safe and stable when administered in a wide range of formulations and doses. In this Phase IIB proposal, GM- 1111 will be further developed as a new therapeutic for the effective treatment of CRS. The overall goal is to advance GM-1111 to an Investigational New Drug (IND) application filing and human clinical trials, which will be accomplished through the completion of IND-enabling safety/toxicology studies in two animal species (Aim 1), GM-1111 drug product stability testing for clinical trial use, and IND application submission (Aim 2).

项目总结