Sulfated Carbohydrates for the Treatment of Periodontitis

摘要 牙周炎影响超过一半的美国人口，并且对于任何阶段和等级的牙周炎都没有可靠的治疗形式。 除了抗生素，牙根刮治和刨平以及牙周手术外，这种疾病的结果差异很大。这 STTR申请提出鉴定结构确定的硫酸化低分子量硫酸乙酰肝素作为新的 用于治疗牙周炎的治疗剂。Glycan Therapeutics LLC是一家专业合成硫酸化 碳水化合物使用创新的酶为基础的方法和生产大量的几种碳水化合物目前 正在被探索用于生物用途。其中一种分子，一种18聚硫酸乙酰肝素，据报道是抗- 我们的小组和初步数据显示了对促进骨稳态的有希望的作用。这 一项建议是集中在调查的具体硫酸化的18聚体长度的碳水化合物作为牙周治疗 在体外和体内。此外，由于研究的碳水化合物被证明是抗炎和骨合成代谢， 性质，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研究 例如在患有糖尿病的受试者中。该小组由帕特里夏·米格兹博士，临床科学家，骨和细胞外 基质生物学家和牙周病学家，UNC-CH的合作者和Glycan的共同研究者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师。这 该提案将提供有价值的见解，这种小的硫酸化碳水化合物在骨中的作用机制 稳态，提供小动物概念验证研究的有效性数据，并为II期提案铺平道路 为了在大型动物模型中评价这种治疗剂用于治疗牙周炎， 和持久的口腔内递送系统。

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.