Kajikawa Tetsuhiro, Mastellos Dimitrios C, Hasturk Hatice, Kotsakis Georgios A, Yancopoulou Despina, Lambris John D, Hajishengallis George
University of Pennsylvania, Penn Dental Medicine, Department of Basic and Translational Sciences, Philadelphia, PA, USA; Tohoku University Graduate School of Dentistry, Department of Periodontology and Endodontology, Sendai, Miyagi, Japan.
National Center for Scientific Research 'Demokritos', Division of Biodiagnostic Sciences and Technologies, INRASTES, Athens, Greece.
Semin Immunol. 2022 Jan;59:101608. doi: 10.1016/j.smim.2022.101608. Epub 2022 Jun 9.
Periodontitis is an inflammatory disease caused by biofilm accumulation and dysbiosis in subgingival areas surrounding the teeth. If not properly treated, this oral disease may result in tooth loss and consequently poor esthetics, deteriorated masticatory function and compromised quality of life. Epidemiological and clinical intervention studies indicate that periodontitis can potentially aggravate systemic diseases, such as, cardiovascular disease, type 2 diabetes mellitus, rheumatoid arthritis, and Alzheimer disease. Therefore, improvements in the treatment of periodontal disease may benefit not only oral health but also systemic health. The complement system is an ancient host defense system that plays pivotal roles in immunosurveillance and tissue homeostasis. However, complement has unwanted consequences if not controlled appropriately or excessively activated. Complement overactivation has been observed in patients with periodontitis and in animal models of periodontitis and drives periodontal inflammation and tissue destruction. This review places emphasis on a promising periodontal host-modulation therapy targeting the complement system, namely the complement C3-targeting drug, AMY-101. AMY-101 has shown safety and efficacy in reducing gingival inflammation in a recent Phase 2a clinical study. We also discuss the potential of AMY-101 to treat peri-implant inflammatory conditions, where complement also seems to be involved and there is an urgent unmet need for effective treatment.
牙周炎是一种由牙齿周围龈下区域生物膜积聚和生态失调引起的炎症性疾病。如果治疗不当，这种口腔疾病可能导致牙齿脱落，进而影响美观、咀嚼功能恶化并降低生活质量。流行病学和临床干预研究表明，牙周炎可能会加重全身性疾病，如心血管疾病、2型糖尿病、类风湿性关节炎和阿尔茨海默病。因此，改善牙周疾病的治疗不仅可能有益于口腔健康，还可能有益于全身健康。补体系统是一种古老的宿主防御系统，在免疫监视和组织稳态中起关键作用。然而，如果补体没有得到适当控制或过度激活，就会产生不良后果。在牙周炎患者和牙周炎动物模型中都观察到补体过度激活，它会引发牙周炎症和组织破坏。本综述重点介绍一种针对补体系统的有前景的牙周宿主调节疗法，即靶向补体C3的药物AMY-101。在最近的一项2a期临床研究中，AMY-101已显示出在减轻牙龈炎症方面的安全性和有效性。我们还讨论了AMY-101治疗种植体周围炎症性疾病的潜力，在这些疾病中补体似乎也有参与，并且迫切需要有效的治疗方法。
