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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.

摘要牙周炎影响超过一半的美国人口，没有可靠的治疗形式来治疗任何阶段和级别的牙周炎。除了抗生素、牙根刮除和平整以及牙周手术外，这种疾病的结果也有很大的不同。这 STTR应用程序建议将结构定义的硫化低分子肝素硫酸盐鉴定为一种新的治疗牙周炎。葡聚糖治疗有限责任公司是一家专门合成硫酸盐的公司碳水化合物使用创新的基于酶的方法，目前生产大量的几种碳水化合物正被探索用于生物用途。据报道，其中一种分子，18-聚硫化乙酰肝素硫酸盐，具有抗肿瘤活性。我们小组的炎症和初步数据显示，在促进骨稳态方面有很好的效果。这提案的重点是研究一种特殊的18聚体碳水化合物作为牙周治疗的方法。在体外和体内。此外，由于研究证明碳水化合物既有抗炎作用，又有骨合成代谢作用自然，它将在高风险和更严重和高度炎症形式的牙周炎的背景下进行调查比如在糖尿病患者中。该团队由帕特里夏·米格斯博士组成，他是临床科学家，骨和细胞外矩阵生物学家和牙周病医生，北卡罗来纳大学-CH分校的合作者，以及来自多糖的共同研究员Vijay Pagadala博士在此类合成低聚糖的合成和表征方面具有丰富经验的治疗学。这该提案将对骨骼中这种小硫酸盐碳水化合物的作用机制提供有价值的见解。动态平衡，在小动物的概念验证研究中提供有效性数据，并为第二阶段提案铺平道路在大动物模型上评价这种治疗牙周炎的方法，并开发一种有效的和持久的口腔内给药系统。