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Sulfated Carbohydrates for the Treatment of Periodontitis

硫酸化碳水化合物治疗牙周炎

基本信息

批准号：
10756240
负责人：
Patricia Miguez
金额：
$ 34.75万
依托单位：
GLYCAN THERAPEUTICS CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10756240
关键词：
Adult Affect Alveolar Bone Loss American Animal Model Animals Anti-Inflammatory Agents Antibiotics Antiinflammatory Effect Autophagocytosis Binding Biological Bone Diseases Bone Morphogenetic Proteins Bone Resorption Calvaria Carbohydrates Cardiovascular system Cells Chronic Clinical Coronary Arteriosclerosis Data Debridement Dependence Development Diabetes Mellitus Disease Disease Management Disease Progression Dose Economic Burden Enzymes Escherichia coli Extracellular Matrix Generations Genes Gingiva Goals HMGB1 gene Health Heparin Heparitin Sulfate Histologic Homeostasis Image Immunocompromised Host In Vitro Infection Inflammation Inflammatory Investigation Kidney Laboratories Learning Length Libraries Ligature Literature Macrophage Measurement Methods Modeling Molecular Weight Mus Nature Oligosaccharides Operative Surgical Procedures Oral Oral cavity Osteoclasts Osteogenesis Outcome Pathogenicity Pathway interactions Performance Periodontal Attachment Loss Periodontal Diseases Periodontitis Periodontium Pharmaceutical Preparations Phase Pilot Projects Polysaccharides Population Predisposition Prevalence Prevention Production Property Protective Agents Publishing Quality of life Refractory Reporting Research Personnel Rheumatoid Arthritis Risk Factors Scientist Signal Transduction Small Business Technology Transfer Research Sulfate System Testing Therapeutic Therapeutic Agents Tissues Tooth Loss Tooth root structure Tooth structure Validation aging population alveolar bone antagonist bone bone cell bone loss chronic inflammatory disease cytokine data acquisition diabetes management diabetic experience experimental study high risk in vitro Assay in vivo innovation insight mouse model novel novel therapeutics osteoclastogenesis osteogenic pathogenic bacteria prevent promoter recruit scaling and root planing standard care tomography

项目摘要

Abstract Periodontitis affects over half of the American population and has no reliable form of treatment for any stage and grade of the disease besides antibiotics, tooth root scaling and planing and periodontal surgery with highly variable outcomes. This STTR application proposes to identify a structurally defined sulfated low molecular weight heparan sulfate as a novel therapeutic for treatment of periodontitis. Glycan Therapeutics LLC is a company specialized in synthesizing sulfated carbohydrates using innovative enzyme-based methods and produce large quantities of several carbohydrates currently being explored for biological use. One of the molecules, an 18-mer sulfated heparan sulfate, has been reported to be anti- inflammatory by our group and preliminary data shows a promising effect on promotion of bone homeostasis. This proposal is focused on the investigation of a specifically sulfated 18-mer length carbohydrate as a periodontal therapeutic in vitro and in vivo. Further, as the carbohydrate investigated proves to be both anti-inflammatory and bone anabolic in nature, it will be investigated in the context of high risk and more severe and hyperinflammatory forms of periodontitis such as in subjects with diabetes. The team consists of Dr. Patricia Miguez, clinician scientist, bone and extracellular matrix biologist and periodontist, and collaborators at UNC-CH and Dr. Vijay Pagadala, co-investigator from Glycan Therapeutics with significant experience in synthesis and characterization of such synthetic oligosaccharides. This proposal will provide valuable insights into the mechanism of action of such small sulfated carbohydrates in bone homeostasis, provide efficacy data in proof-of-concept studies in small animals and pave the way for a phase II proposal to evaluate such therapeutic for treatment of periodontitis in a large animal model and with development of an efficient and long-lasting intra-oral delivery system.

抽象的牙周炎影响了一半以上的美国人，并且对于任何阶段和级别的牙周炎都没有可靠的治疗方法除了抗生素、牙根刮治和牙周手术外，这种疾病的治疗结果差异很大。这 STTR 申请旨在鉴定结构明确的硫酸化低分子量硫酸乙酰肝素作为新型用于治疗牙周炎的治疗剂。 Glycan Therapeutics LLC 是一家专业合成硫酸化药物的公司使用创新的基于酶的方法生产碳水化合物，目前可大量生产多种碳水化合物正在探索其生物学用途。据报道，其中一种分子是 18 聚体硫酸化乙酰肝素，具有抗- 我们小组的炎症研究和初步数据表明，它对促进骨稳态具有良好的作用。这该提案的重点是研究一种专门硫酸化的 18 聚体长度碳水化合物作为牙周治疗剂体外和体内。此外，由于所研究的碳水化合物被证明具有抗炎和骨合成代谢作用本质上，它将在高风险、更严重和高炎症形式的牙周炎的背景下进行研究例如糖尿病患者。该团队由骨和细胞外临床科学家 Patricia Miguez 博士组成基质生物学家和牙周病学家、UNC-CH 的合作者以及 Glycan 的联合研究员 Vijay Pagadala 博士在此类合成寡糖的合成和表征方面具有丰富经验的治疗方法。这该提案将为了解这种小硫酸化碳水化合物在骨骼中的作用机制提供有价值的见解稳态，提供小动物概念验证研究的功效数据，并为第二阶段提案铺平道路在大型动物模型中评估这种治疗方法对牙周炎的治疗效果，并开发一种有效的方法和持久的口腔内输送系统。