Promore Pharma AB, Karolinska Institutet Science Park, Solna, Sweden.
RISE Research Institutes of Sweden, Borås, Sweden.
Crit Rev Biotechnol. 2020 Nov;40(7):978-992. doi: 10.1080/07388551.2020.1796576. Epub 2020 Aug 12.
The rapid development of microbial resistance to conventional antibiotics has accelerated efforts to find anti-infectives with a novel mode-of-action, which are less prone to bacterial resistance. Intense nonclinical and clinical research is today ongoing to evaluate antimicrobial peptides (AMPs) as potential next-generation antibiotics. Currently, multiple AMPs are assessed in late-stage clinical trials, not only as novel anti-infective drugs, but also as innovative product candidates for immunomodulation, promotion of wound healing, and prevention of post-operative scars. The efforts to translate AMP-based research findings into pharmaceutical product candidates are expected to accelerate in coming years due to technological advancements in multiple areas, including an improved understanding of the mechanism-of-action of AMPs, smart formulation strategies, and advanced chemical synthesis protocols. At the same time, it is recognized that cytotoxicity, low metabolic stability due to sensitivity to proteolytic degradation, and limited oral bioavailability are some of the key weaknesses of AMPs. Furthermore, the pricing and reimbursement environment for new antimicrobial products remains as a major barrier to the commercialization of AMPs.
微生物对传统抗生素的耐药性迅速发展,加速了寻找具有新型作用模式的抗感染药物的努力,这些药物不易产生细菌耐药性。目前正在进行大量的非临床和临床研究,以评估抗菌肽 (AMP) 作为潜在的下一代抗生素。目前,多种 AMP 正在进行后期临床试验评估,不仅作为新型抗感染药物,还作为免疫调节、促进伤口愈合和预防术后疤痕的创新产品候选物。由于多个领域的技术进步,包括对 AMP 作用机制的更深入理解、智能配方策略和先进的化学合成方案,预计基于 AMP 的研究成果转化为药物产品候选物的工作将在未来几年加速。与此同时,人们认识到细胞毒性、由于对蛋白水解降解的敏感性导致的低代谢稳定性以及有限的口服生物利用度是 AMP 的一些关键弱点。此外,新抗菌产品的定价和报销环境仍然是 AMP 商业化的主要障碍。