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:
- 金额:$ 34.75万
- 依托单位:
- 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:
- 关键词:AdultAffectAlveolar Bone LossAmericanAnimal ModelAnimalsAnti-Inflammatory AgentsAntibioticsAntiinflammatory EffectAutophagocytosisBindingBiologicalBone DiseasesBone Morphogenetic ProteinsBone ResorptionCalvariaCarbohydratesCardiovascular systemCellsChronicClinicalCoronary ArteriosclerosisDataDebridementDependenceDevelopmentDiabetes MellitusDiseaseDisease ManagementDisease ProgressionDoseEconomic BurdenEnzymesEscherichia coliExtracellular MatrixGenerationsGenesGingivaGoalsHMGB1 geneHealthHeparinHeparitin SulfateHistologicHomeostasisImageImmunocompromised HostIn VitroInfectionInflammationInflammatoryInvestigationKidneyLaboratoriesLearningLengthLibrariesLigatureLiteratureMacrophageMeasurementMethodsModelingMolecular WeightMusNatureOligosaccharidesOperative Surgical ProceduresOralOral cavityOsteoclastsOsteogenesisOutcomePathogenicityPathway interactionsPerformancePeriodontal Attachment LossPeriodontal DiseasesPeriodontitisPeriodontiumPharmaceutical PreparationsPhasePilot ProjectsPolysaccharidesPopulationPredispositionPrevalencePreventionProductionPropertyProtective AgentsPublishingQuality of lifeRefractoryReportingResearch PersonnelRheumatoid ArthritisRisk FactorsScientistSignal TransductionSmall Business Technology Transfer ResearchSulfateSystemTestingTherapeuticTherapeutic AgentsTissuesTooth LossTooth root structureTooth structureValidationaging populationalveolar boneantagonistbonebone cellbone losschronic inflammatory diseasecytokinedata acquisitiondiabetes managementdiabeticexperienceexperimental studyhigh riskin vitro Assayin vivoinnovationinsightmouse modelnovelnovel therapeuticsosteoclastogenesisosteogenicpathogenic bacteriapreventpromoterrecruitscaling and root planingstandard caretomography
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。
项目成果
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Patricia Miguez的其他文献
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