Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany.
German Center for Cardiovascular Research (DZHK), partner site Göttingen, Göttingen, Germany.
J Cachexia Sarcopenia Muscle. 2020 Feb;11(1):274-285. doi: 10.1002/jcsm.12552.
This article highlights preclinical and clinical studies in the field of wasting disorders that were presented at the 12th Cachexia Conference held in Berlin, Germany, in December 2019. Herein, we summarize the biological and clinical significance of different strategies including antibodies that target Fn14, Spsb 1, SAA1 treatment, ZIP14, a MuRF1 inhibitor, and new diagnostic tools like T-cell communication targets and cut-offs for the detection of skeletal muscle wasting. Of particular interest were the transplantation of mesenchymal stromal cells and muscle stem cell communication. Importantly, one presentation discussed the effect of metal ion transporter ZIP14 loss that reduces cancer-induced cachexia. The potential of anti-ZIP14 antibodies and zinc chelation as anti-cachexia therapy may require testing in patients with cancer cachexia. Large clinical studies were presented such as RePOWER (observational study of patients with primary mitochondrial myopathy), MMPOWER (treatment with elamipretide in patients with primary mitochondrial myopathy), and ACT-ONE as well as new mouse models like the KPP mouse. Promising treatments include rapamycin analogue treatment, anamorelin, elanapril, glucocorticoids, SAA1, antibodies that target Fn14, and a MuRF1 inhibitor. Clinical studies investigated novel approaches, including the role of exercise. It remains a fact, however, that effective treatments for cachexia and wasting disorders are urgently needed in order to improve patients' quality of life and their survival.
本文重点介绍了在 2019 年 12 月于德国柏林举行的第十二届恶病质会议上展示的消耗性疾病领域的临床前和临床研究。在此,我们总结了不同策略的生物学和临床意义,包括针对 Fn14、Spsb1、SAA1 治疗、ZIP14、MuRF1 抑制剂的抗体以及新的诊断工具,如 T 细胞通讯靶点和用于检测骨骼肌消耗的截止值。特别值得关注的是间充质基质细胞和肌肉干细胞通讯的移植。重要的是,有一个报告讨论了金属离子转运蛋白 ZIP14 缺失对减少癌症引起的恶病质的影响。抗 ZIP14 抗体和锌螯合作为抗恶病质疗法的潜力可能需要在癌症恶病质患者中进行测试。大型临床试验如 RePOWER(原发性线粒体肌病患者的观察性研究)、MMPOWER(原发性线粒体肌病患者用 elamipretide 治疗)和 ACT-ONE 以及 KPP 小鼠等新的小鼠模型进行了介绍。有前途的治疗方法包括雷帕霉素类似物治疗、anamorelin、elanapril、糖皮质激素、SAA1、针对 Fn14 的抗体和 MuRF1 抑制剂。临床研究调查了新的方法,包括运动的作用。然而,事实上,迫切需要有效的恶病质和消耗性疾病治疗方法,以提高患者的生活质量和生存率。