Testing safety of novel combination therapeutics that overcome antimicrobial resistance in Pseudomonas aeruginosa infections and reduce treatment-associated side effects.

自从发现青霉素以来，抗生素改变了世界各地的生活，使100年前致命的细菌感染变得容易治疗。然而，滥用抗生素导致对抗生素产生抗药性的细菌感染迅速上升，因此非常难以抗击。抗菌素耐药(AMR)感染有可能成为下一次大流行，预计到2050年每年将导致1000万人死亡，使AMR成为我们这个时代最大的医疗挑战之一，需要紧急解决。然而，在这一关键领域，由于将依赖于昂贵研究计划的传统药物发现方法应用于抗生素的经济困难，研发活动的水平低得危险。众所周知，抗生素缺乏有利的定价和报销模式。美杜莎制药公司正在开发一种新的方法来解决AMR。我们不再追求缓慢、危险和昂贵的过程来尝试发现新的抗生素，而是重新调整已经获得批准并在临床上使用的药物的用途，以重振现有的抗生素并提高它们的疗效，呈现出强大的协同联合疗法。通过以最佳组合使用这些药物，我们可以克服对抗生素的耐药性，从而对抗目前无法治愈的AMR感染。此外，我们的方法意味着我们将能够减少在慢性感染中对抗细菌所需的抗生素剂量，从而减少其浓度依赖的副作用，这些副作用越来越受到长期使用者的关注。我们的方法有可能定义一种对抗AMR的新范式。我们将利用几十年来关于已经批准的成分分子的数据，大幅降低研发成本，加快临床应用，为应对日益增长的AMR全球挑战提供一个风险较低且易于部署的解决方案，以拯救世界各地的生命。该项目将专门研究构成我们工作基础的令人信服的学术发现的翻译适用性，确定最佳有效化合物(针对主要目标病原体_铜绿假单胞菌_)在人类细胞中的安全性/毒性概况。我们将测试增效化合物的先导组合，以在人类细胞系模型中调查安全性，提供毒性曲线，并表明将这项工作推进到临床前体内测试的潜力。该项目在加速临床开发的道路上是绝对关键的早期步骤。

Since the discovery of Penicillin, antibiotics have transformed lives across the world, making bacterial infections that were lethal just 100 years ago straightforward to treat. However, misuse of antibiotics has resulted in a rapid rise in bacterial infections that are resistant to antibiotics and thus very difficult to combat. Antimicrobial resistant (AMR) infections have the potential to become the next pandemic, predicted to kill 10 million people per year by 2050, making AMR one of the greatest healthcare challenges of our time, calling for an urgent solution. However there is a dangerously low level of R&D activity in this critical space due to the economic difficulty of applying traditional drug discovery approaches, that rely on costly research programmes, to antibiotics which notoriously lack favourable pricing and reimbursement models.Medusa Pharmaceuticals is developing a new approach to tackle AMR. Instead of pursuing the slow, risky and expensive process of attempting to discover new antibiotics, we are repurposing drugs that are already approved and used in the clinic to reinvigorate existing antibiotics and increase their efficacy, presenting powerful synergistic combination therapeutics. By administering these drugs in optimal combinations we can overcome resistance to antibiotics and thereby combat currently untreatable AMR infections. Moreover, our approach means that we will be able to reduce the doses of antibiotics that are required to fight bacteria in chronic infections too, thus reducing their concentration-dependent side effects that are of increasing concern to long term users. Our approach has the potential to define a new paradigm to combat AMR. We will be leveraging decades of data on the already approved component molecules, presenting a substantially reduced R&D cost and accelerated time to clinic, for a de-risked and readily deployable solution to the rising global challenge of AMR, to save lives all around the world.This project will specifically investigate the translational applicability of the compelling academic discovery that forms the basis of our work, determining the safety/toxicity profile of optimally efficacious compounds (against primary target pathogen, _Pseudomonas aeruginosa_) in human cells. We will be testing lead combinations of synergistic compounds to investigate safety in human cell line models, to provide the toxicity profile and indicate potential to take this work forward to pre-clinical _in vivo_ testing. This project is an absolutely crucial early step in an accelerated pathway to clinical development.