背景:心力衰竭是全球主要的健康问题和死亡的主要原因。由于其脱靶效应和缺乏特异性,RNAi干预对于对常规药物具有抗性的患者具有希望。
目的:研究RNAi治疗心力衰竭的安全性和有效性。
方法:PubMed,Embase,从开始到2023年12月31日,使用适当的关键字搜索Scopus和Cochrane数据库。共有14项符合预定选择标准的研究被纳入定性综合。
结果:我们发现,在心脏淀粉样变性患者中,patisiran和revusiran显示心输出量和左心室壁厚度显著改善.在动物研究中,Nox2-siRNA显示了恢复心脏功能的有效性。此外,心肌梗死(MI)后,DUSP5siRNAT3治疗和meg3抑制可改善心肌细胞计数和左心室功能。RNAi显示最小的副作用,如周围神经病变,肝毒性,尿路感染,阴道感染,腹泻,腹痛心律失常,传导障碍,和心脏毒性(左心室壁变薄,心力衰竭)和改善的心脏生物标志物。
结论:RNAi疗法是改善心脏功能的新型治疗选择,因为它们具有较高的靶特异性,靶向基因的能力,传统药物难以达到和潜在的持久的影响。进一步研究优化交付方式,提高目标特异性,评估长期安全概况和成本效益,以充分发挥其潜力。
BACKGROUND: Heart failure is a major worldwide health concern and leading cause of mortality. RNAi interventions hold promise for patients resistant to conventional drugs due to their off-target effects and lack of specificity.
OBJECTIVE: To examine the safety and effectiveness of RNAi therapeutics in treating heart failure.
METHODS: The PubMed, Embase, Scopus and Cochrane databases were searched using appropriate keyword from inception until December 31, 2023. A total of 14 studies fulfilling predefined selection criteria were included for qualitative synthesis.
RESULTS: We found that in patients with cardiac amyloidosis, patisiran and revusiran showed considerable improvements in cardiac output and left ventricular wall thickness. In animal studies, Nox2-siRNA showed effectiveness in regaining heart function. Furthermore, cardiomyocyte count and left ventricular function were improved by DUSP5 siRNA + T3 therapy and meg3 inhibition after myocardial infarction (MI). RNAi showed minimal adverse effects like peripheral neuropathy, hepatotoxicity, urinary tract infection, vaginal infection, diarrhea, abdominal pain arrhythmias, conduction disorders, and cardiotoxicity (LV wall thinning, heart failure) and improved cardiac biomarkers.
CONCLUSIONS: RNAi therapeutics are novel treatment option for improving cardiac function because their high target specificity, ability to target genes that conventional drugs struggle to reach and potential for long-lasting effects. Further research on optimizing delivery methods, improving target specificity, evaluating long-term safety profiles and cost-effectiveness to fully realize their potential.