A Novel Remedy for Periodontal Bone Loss

治疗牙周骨质流失的新疗法

基本信息

批准号：
10705278
负责人：
Xin Li
金额：
$ 101.72万
依托单位：
PERIOMICS CARE, LLC
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10705278
关键词：
Adult Affect Alveolar Bone Loss American Dental Association Antibiotics Antimicrobial Resistance Biological Products Biotechnology Bone Resorption Calculi Canis familiaris Caring Chronic Clinical Treatment Clinical Trials Collaborations Conduct Clinical Trials Data Debridement Dental Clinics Dental Plaque Dentistry Dentists Development Disadvantaged Dose Doxycycline Drug Kinetics Drug Targeting Esthetics Failure Formulation Funding Gel Gingiva Gingival Pocket Grant Growth Health Home Human Immune response In Vitro Inflammation Inflammatory Response Intellectual Property International Investments Knockout Mice Lasers Legal patent Letters Licensing Ligature Local Therapy Macaca mulatta Manuscripts Marketing Mechanics Microbial Biofilms Modeling Mus New York Oral Oral health Osteoclasts Outcome Study Pain Pathogenesis Pathway interactions Patients Penetration Periodontal Diseases Periodontal Ligament Periodontitis Periodontium Pharmacodynamics Phase Physiological Population Pre-Clinical Model Prevalence Prevention Process Quality of life Receptor Activation Research Risk Series Small Business Technology Transfer Research Standardization Structure Study models Succinates Surface Symptoms Technology Testing Therapeutic Tissues Tooth Loss Tooth structure Toothpaste Topical application Toxic effect Treatment Protocols Vision Visit aged alveolar bone antagonist antimicrobial bone bone loss chronic inflammatory disease college commercialization cost effective efficacy evaluation experience human disease in vivo metabolomics mouse model nonhuman primate novel oral pathogen pathobiont pathogen pathogenic microbe phase 1 study phase 2 study prevent receptor response scale up scaling and root planing side effect subgingival microbiome

项目摘要

Periodontitis is a common chronic inflammatory disease characterized by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). The total prevalence of periodontitis in adults aged 30 years and older was 47.2% (representing about 64.7 million adults aged 30 years and older) and 70.1% in adults aged 65 years and older in the U.S. The current treatment option for periodontal diseases involves mechanical debridement – scaling and root planing which requires frequent and multiple visits to the dentist and is sometimes followed by adjunctive therapy of local delivery of antimicrobials or systemic antibiotics such as doxycycline. The disadvantages of current treatment options are inconvenient and painful experience, failure of antimicrobial to penetrate beyond biofilm surface layer, risks to promote antimicrobial resistance, and systemic side effects. Other limitation of current treatment is that none of these drugs are targeting host and periodontal bone loss. There is a major void in periodontal disease therapeutics products which can target host response and is easy to use. The global periodontal disease therapeutics market is anticipated to gain a growth of 8.7% from 2016 to 2024. At this pace, the market is estimated to reach a valuation of US$537.2M by the end of the forecast period. Periomics Care is an early-stage New York based biotechnology company that was established to commercialize a novel oral gel formulation for treatment of periodontal disease. In Phase I we have synthesized, formulated, tested and patented POC7a, an antagonist formulation to target succinate receptor (SUCNR1) as a treatment for periodontal disease. In Phase II Periomics Care proposes to scale up the synthesis and formulation of POC7a to conduct pharmacokinetics/ pharmacodynamics, and toxicity of POC7a in Beagle dogs (Aim1). We will further test this formulation in ligature induced Non-human Primate (NHP) model to validate our finding that POC7a effectively rescues periodontal bone loss (Aim 2). NHP model is the best suitable model for this study because they have a high degree of resemblance in terms of pathways of physiological responses and targets that are relevant to human disease. More importantly NHP have oral structures and teeth similar to those of humans and have naturally occurring dental plaque, calculus, oral microbial pathogens and develop similar periodontal symptoms. The premise of this proposal is based on our findings in Phase I that blocking SUCNR1 by POC7a can reduce inflammation, alter subgingival microbiome and rescue bone loss. The technology and formulation developed in Phase I is now IP protected. The funds gained from this STTR Phase II grant will be used for (1) synthesis and testing of the formulation, and (2) determining the efficacy of the formulation in periodontal NHP model. The outcomes from this study will help the company to seek FDA approval for the optimal formulation and conduct clinical trials for the treatment and prevention of periodontal disease.

牙周炎是一种常见的慢性炎症性疾病，其特征是支持牙周组织的破坏牙齿的结构（牙周韧带和牙槽骨）。 30岁及以上的成年人为47.2%（约占30岁及以上的6,470万成年人）在美国，65 岁及以上的成年人中，这一比例为 70.1% 目前牙周病的治疗选择涉及机械清创 – 刮治和根部平整，需要频繁且多次访问牙医有时会进行局部抗菌药物或全身给药的辅助治疗目前治疗方案的缺点是不方便且痛苦。经验、抗菌剂未能穿透生物膜表面层、推广抗菌剂的风险目前治疗的其他限制是这些药物都不是。针对宿主和牙周骨质流失的牙周病治疗产品存在重大空白。它可以针对宿主响应并且易于使用。预计2016年至2024年全球牙周病治疗市场将增长8.7%。按照这个速度，到预测期结束时，市场估值预计将达到 5.372 亿美元。 Periomics Care 是一家总部位于纽约的早期生物技术公司，成立的目的是在第一阶段，我们将用于治疗牙周病的新型口腔凝胶制剂商业化。合成、配制、测试并获得专利的 POC7a，一种针对琥珀酸受体的拮抗剂制剂（SUCNR1）作为牙周病的治疗方法，在 II 期 Periomics Care 中建议扩大规模。 POC7a的合成和配制以进行药代动力学/药效学以及POC7a的毒性我们将在结扎诱导的非人类灵长类动物 (NHP) 中进一步测试该配方。模型来验证我们的发现，即 POC7a 可以有效挽救牙周骨质流失（目标 2）。最适合本研究的模型，因为它们在路径方面具有高度相似性与人类疾病相关的生理反应和目标更重要的是NHP具有口服作用。结构和牙齿与人类相似，并且具有天然存在的牙菌斑、牙石、口腔微生物病原体并出现类似的牙周症状是基于我们的前提。 I 期研究结果表明，通过 POC7a 阻断 SUCNR1 可以减少炎症、改变龈下微生物组第一阶段开发的技术和配方现已受到知识产权保护。从 STTR 第二阶段拨款中获得的资金将用于 (1) 配方的合成和测试，以及 (2) 这项研究的结果将有助于确定该制剂在牙周 NHP 模型中的功效。该公司正在寻求 FDA 批准最佳配方并进行治疗和临床试验预防牙周病。