A Novel Remedy for Periodontal Bone Loss

治疗牙周骨质流失的新疗法

• 批准号: 10481946
• 负责人: Xin Li
• 金额: $ 59.11万
• 依托单位: PERIOMICS CARE, LLC
• 依托单位国家: 美国
• 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/10481946
• 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; Mechanics; Microbial Biofilms; Modeling; Mus; New York; Oral; Oral health; Osteoclasts; Outcome Study; Pain; Pathogenesis; Pathway interactions; Patients; Periodontal Diseases; Periodontal Ligament; Periodontitis; Periodontium; Pharmacodynamics; Phase; Physiological; Population; Pre-Clinical Model; Prevalence; Prevention; Process; Quality of life; Receptor Activation; Research; Risk; Seeds; 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; base; bone; bone loss; chronic inflammatory disease; college; cost effective; experience; human disease; in vivo; metabolomics; mouse model; nonhuman primate; novel; oral pathogen; pathobiont; pathogen; pathogenic microbe; pharmacokinetics and pharmacodynamics; phase 1 study; phase 2 study; prevent; receptor; response; scale up; scaling and root planing; side effect; subgingival microbiome

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以支撑体破坏为特征的慢性炎症性疾病 牙齿的结构(牙周膜和牙槽骨)。年牙周炎总患病率 30岁及以上的成年人占47.2%(约6470万30岁及以上的成年人) 在美国65岁及以上的成年人中有70.1%。目前牙周病的治疗选择 涉及机械清创--刮除和根面平整，这需要频繁和多次访问 牙科医生，有时还会辅以局部给药或全身用药 多西环素等抗生素。目前的治疗方案的缺点是不方便和痛苦 经验，抗菌剂未能穿透生物膜表层，推广抗菌剂的风险 耐药性和系统性副作用。目前治疗的另一个局限性是，这些药物都不是 靶向宿主和牙周骨丢失。牙周病治疗产品中存在一个重大空白 它可以针对主机响应，并且易于使用。 从2016年到2024年，全球牙周病治疗药物市场预计将增长8.7%。 按照这一速度，预计到预测期结束时，市场估值将达到5.372亿美元。 PeriEconomics Care是一家总部位于纽约的早期生物技术公司，成立目的是 商业化一种治疗牙周病的新型口腔凝胶配方。在第一阶段，我们有 针对琥珀酸受体的拮抗剂POC7a的合成、配制、测试和专利申请 (SUCNR1)作为治疗牙周病的药物。在第二阶段，PeriEconomics Care建议扩大 POC7a的合成及其用于药代动力学/药效学和毒性的研究 在Beagle狗身上(Aim1)。我们将在结扎诱导的非人灵长类动物(NHP)中进一步测试这一配方。 模型，以验证我们的发现，POC7a有效地挽救牙周骨丢失(目标2)。NHP模式是 最适合这项研究的模型，因为它们在以下方面具有高度的相似性 与人类疾病相关的生理反应和靶点。更重要的是，NHP有口头 与人类相似的结构和牙齿，具有自然形成的牙菌斑、牙石、口腔 病原体和发展类似的牙周症状。这项建议的前提是基于我们的 一期研究发现，POC7a阻断SUCNR1可以减轻炎症，改变龈下微生物群 并挽救骨质流失。第一阶段开发的技术和配方现在受到知识产权保护。这些资金 从STTR第二阶段赠款中获得的资金将用于(1)配方的合成和测试，以及(2) 测定该制剂在牙周NHP模型中的疗效。这项研究的结果将会有所帮助 该公司将寻求FDA批准最佳配方，并进行治疗和临床试验 预防牙周病。