Development of clinically translatable therapies for the treatment and prevention of bacterial vaginosis

开发用于治疗和预防细菌性阴道病的临床可转化疗法

• 批准号: 105742
• 金额: $ 25.12万
• 依托单位: CC BIOTECH LTD.
• 依托单位国家: 英国
• 项目类别: Study
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=105742
• 关键词: Development; clinically; translatable; therapies; treatment

This research aims to develop new therapies for the treatment of recurrent bacterial vaginosis (BV). BV is the most common vaginal infection experienced by women of childbearing age, with up to 30% of woman of this group affected by the condition. BV is caused by the overgrowth of unwanted bacteria within the vagina. The main problematic bacterium which causes BV is called Gardnerella vaginalis. Introduced from sexual contact, the GI tract or through other activities such as vaginal douching, this bacterium colonises the vagina, destroying the healthy, natural bacteria which normally live in the vaginal environment. Literature studies have shown that G. vaginalis grows as part of a sticky bacterial structure known as a biofilm: it provides the initial structure for this biofilm which attracts other vaginal pathogens.While only a minority of women infected with G. vaginalis (1/6th of carriers) display psychologically distressing symptoms of BV (foul-fishy odour/grey white discharge), all carriers of the condition face increased risks of STI transmission, miscarriage (ten-fold increase) and preterm birth (doubled risk).The most common treatment for BV is the prescription of antibiotics. However, while relieving symptoms temporarily, antibiotics don't prevent BV recurrence. 70% of all BV patients treated with antibiotics experience recurrence of BV within 9 months. Many women experience thrush following usage of antibiotics for BV, and there are a number of reports of antibiotic resistant Gardnerella vaginalis. These issues illustrate that BV is poorly managed by traditional antibiotics, likely because they fail to fully destroy the G. vaginalis biofilm.In this project, we will develop therapies which selectively target and destroy Gardnerella vaginalis, unlike existing antibiotics which are not targeted, and kill healthy bacteria non-selectively. Our therapeutics will effectively treat the condition, by destroying Gardnerella vaginalis growing in biofilm. This is in contrast to current antibiotics, which cannot currently penetrate and destroy these biofilms, resulting in regrowth after completion of therapy, leading to recurrence.The low likelihood of Gardnerella developing resistance to our new therapies will allow their preventative usage as a prenatal health aid, which is not possible for current therapies. This will reduce the rate of miscarriages/premature births associated with the condition.The research detailed in this project will primarily be conducted by CC Biotech Ltd, in association with collaborator academic institutions, with assistance from leading UK contractor organisations.At project conclusion, we will have developed candidate therapies which are ready for animal safety/efficacy studies/human clinical trials.

本研究旨在开发治疗复发性细菌性阴道病(BV)的新疗法。BV是育龄妇女经历的最常见的阴道感染，这一群体中高达30%的妇女受到这种情况的影响。BV是由阴道内多余的细菌过度生长引起的。引起BV的主要问题细菌是阴道加德纳氏菌。这种细菌通过性接触、胃肠道或其他活动，如阴道冲洗，在阴道内定植，摧毁通常生活在阴道环境中的健康、自然的细菌。文献研究表明，阴道毛滴虫是作为一种称为生物膜的粘性细菌结构的一部分生长的：它为这种吸引其他阴道病原体的生物膜提供了初始结构。虽然只有少数感染阴道毛滴虫的女性(1/6的携带者)表现出令人痛苦的BV(恶臭/灰色白色分泌物)心理症状，但所有这种情况的携带者都面临着STI传播、流产(增加10倍)和早产(风险增加一倍)的风险增加。BV最常见的治疗方法是开抗生素处方。然而，虽然抗生素暂时缓解了症状，但并不能防止BV的复发。在所有接受抗生素治疗的BV患者中，70%的患者在9个月内复发。许多女性在使用抗生素治疗BV后会出现鹅口疮，有一些报告显示阴道加德纳菌具有抗药性。这些问题表明，传统抗生素对BV的管理不善，可能是因为它们未能完全破坏阴道加德纳菌的生物膜。在这个项目中，我们将开发有选择性地靶向并摧毁阴道加德纳菌的疗法，而不是现有的无靶向的抗生素，并非选择性地杀死健康的细菌。我们的疗法将有效地治疗这种情况，通过摧毁生长在生物膜中的阴道加德纳氏菌。这与目前的抗生素形成鲜明对比，目前抗生素无法穿透和破坏这些生物膜，导致治疗完成后重新生长，导致复发。加德纳氏菌对我们的新疗法产生抗药性的可能性很低，这将允许将其作为产前保健辅助手段进行预防性使用，这对目前的疗法是不可能的。这将减少与这种情况有关的流产/早产的比率。这个项目中详细的研究将主要由CC Biotech Ltd与合作的学术机构合作进行，并得到领先的英国承包商组织的帮助。在项目结束时，我们将开发出可用于动物安全性/有效性研究/人类临床试验的候选疗法。