Caicedo Andrés, Morales Emilia, Moyano Aldana, Peñaherrera Sebastian, Peña-Cisneros José, Benavides-Almeida Abigail, Pérez-Meza Álvaro A, Haro-Vinueza Alissen, Ruiz Cristina, Robayo Paola, Tenesaca Doménica, Barba Diego, Zambrano Kevin, Castañeda Verónica, Singh Keshav K
Universidad San Francisco de Quito USFQ, Colegio de Ciencias de la Salud, Escuela de Medicina, Quito, Ecuador; Universidad San Francisco de Quito USFQ, Instituto de Investigaciones en Biomedicina iBioMed, Quito, Ecuador; Mito-Act Research Consortium, Quito, Ecuador; Sistemas Médicos SIME, Universidad San Francisco de Quito, Quito, Ecuador.
Universidad San Francisco de Quito USFQ, Instituto de Investigaciones en Biomedicina iBioMed, Quito, Ecuador; Mito-Act Research Consortium, Quito, Ecuador; Biología, Colegio de Ciencias Biológicas y Ambientales COCIBA, Universidad San Francisco de Quito USFQ, Quito, Ecuador.
Pharmacol Res. 2024 Jan;199:107018. doi: 10.1016/j.phrs.2023.107018. Epub 2023 Nov 25.
Mitochondria's role as engines and beacons of metabolism and determinants of cellular health is being redefined through their therapeutic application as "Living Drugs" (LDs). Artificial mitochondrial transfer/transplant (AMT/T), encompassing various techniques to modify, enrich, or restore mitochondria in cells and tissues, is revolutionizing acellular therapies and the future of medicine. This article proposes a necessary definition for LDs within the Advanced Therapeutic Medicinal Products (ATMPs) framework. While recognizing different types of LDs as ATMPs, such as mesenchymal stem cells (MSCs) and chimeric antigen receptor T (CAR T) cells, we focus on mitochondria due to their unique attributes that distinguish them from traditional cell therapies. These attributes include their inherent living nature, diverse sources, industry applicability, validation, customizability for therapeutic needs, and their capability to adapt and respond within recipient cells. We trace the journey from initial breakthroughs in AMT/T to the current state-of-the-art applications by emerging innovative companies, highlighting the need for manufacturing standards to navigate the transition of mitochondrial therapies from concept to clinical practice. By providing a comprehensive overview of the scientific, clinical, and commercial landscape of mitochondria as LDs, this article contributes to the essential dialogue among regulatory agencies, academia, and industry to shape their future in medicine.
线粒体作为新陈代谢的引擎和灯塔以及细胞健康的决定因素，正通过其作为“活药物”（LDs）的治疗应用而被重新定义。人工线粒体转移/移植（AMT/T）涵盖了多种用于修饰、富集或恢复细胞和组织中线粒体的技术，正在彻底改变无细胞疗法和医学的未来。本文在高级治疗药品（ATMPs）框架内对LDs提出了必要的定义。虽然认识到不同类型的LDs属于ATMPs，如间充质干细胞（MSCs）和嵌合抗原受体T（CAR T）细胞，但我们关注线粒体是因为它们具有与传统细胞疗法不同的独特属性。这些属性包括其固有的生命本质、多样的来源、行业适用性、验证性、可根据治疗需求定制以及在受体细胞内适应和响应的能力。我们追溯了从AMT/T的最初突破到新兴创新公司当前最先进应用的历程，强调了制造标准对于引导线粒体疗法从概念向临床实践转变的必要性。通过全面概述线粒体作为LDs的科学、临床和商业前景，本文有助于监管机构、学术界和行业之间就塑造其医学未来展开至关重要的对话。
