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

自青霉素被发现以来，抗生素已经改变了世界各地的生活，使100年前致命的细菌感染变得简单易治。然而，滥用抗生素导致对抗生素具有耐药性的细菌感染迅速增加，因此很难防治。抗生素耐药性（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保健挑战之一，需要紧急解决方案。然而，由于将传统的药物发现方法应用于抗生素的经济困难，这一关键领域的研发活动水平非常低，这些方法依赖于昂贵的研究计划，而抗生素众所周知缺乏有利的定价和报销模式。Medusa Pharmaceuticals正在开发一种新的方法来解决AMR。我们不再追求缓慢、冒险和昂贵的过程来尝试发现新的抗生素，而是重新利用已经批准并在临床上使用的药物，以重振现有的抗生素并提高其疗效，从而提供强大的协同组合疗法。通过以最佳组合施用这些药物，我们可以克服对抗生素的耐药性，从而对抗目前无法治疗的AMR感染。此外，我们的方法意味着我们将能够减少对抗慢性感染细菌所需的抗生素剂量，从而减少长期使用者日益关注的浓度依赖性副作用。我们的方法有可能定义一个新的范式来对抗AMR。我们将利用数十年来已批准的组分分子的数据，大幅降低研发成本，加快临床时间，为日益严峻的AMR全球挑战提供低风险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引人注目的学术发现的转化适用性，确定最佳有效化合物（针对主要目标病原体_铜绿假单胞菌_）在人细胞中的安全性/毒性特征。我们将测试协同化合物的主要组合，以研究人类细胞系模型中的安全性，提供毒性特征，并表明将这项工作推进到临床前体内测试的潜力。该项目是加速临床开发过程中至关重要的早期步骤。

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.