Gene Therapy for Heart Failure: New Perspectives.
Gene Therapy for Heart Failure: New Perspectives.
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DOI：
10.1007/s11897-018-0410-z
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发表时间：
2018-12
影响因子：
--
通讯作者：
Recchia FA
中科院分区：
文献类型：
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作者：
Gabisonia K;Recchia FA
目前关于心衰（HF）发生和发展的病理生理和分子机制的知识是非常丰富的。然而，实验结果和治疗选择之间的差距仍然太大，而现有的药物治疗大多是经验丰富的，疗效有限。早在许多年前，研究人员就提出了心衰的基因治疗方案，因为有必要确定新的非药物策略来靶向分子改变。在这里，我们将回顾过去几年提出的一些策略，以针对导致严重心脏损伤发展为心力衰竭的主要致病机制/因素，并将提供支持保持这一主题研究的必要性的论据。经过几十年的临床前研究和热情与失望的阶段，近年来终于启动了临床试验。第一个进入II期并测试肌内质网钙atp酶基因传递的试验并没有产生令人鼓舞的结果，然而其他试验正在进行中，更有效的病毒载体正在开发中，并且已经确定了有希望的新的潜在靶点。例如，最近的研究集中在体内的基因修复，以治疗遗传性HF，而强有力的实验证据表明，特定的microrna可以传递到缺血后的心脏以诱导再生，这一结果以前被认为只有通过干细胞治疗才有可能实现。心衰的基因治疗正在老化，但令人兴奋的前景仍然非常开放。
The current knowledge of pathophysiological and molecular mechanisms responsible for the genesis and development of heart failure (HF) is absolutely vast. Nonetheless, the hiatus between experimental findings and therapeutic options remains too deep, while the available pharmacological treatments are mostly seasoned and display limited efficacy. The necessity to identify new, non-pharmacological strategies to target molecular alterations led investigators, already many years ago, to propose gene therapy for HF. Here, we will review some of the strategies proposed over the past years to target major pathogenic mechanisms/factors responsible for severe cardiac injury developing into HF and will provide arguments in favor of the necessity to keep alive research on this topic. After decades of preclinical research and phases of enthusiasm and disappointment, clinical trials were finally launched in recent years. The first one to reach phase II and testing gene delivery of sarcoendoplasmic reticulum calcium ATPase did not yield encouraging results, however other trials are ongoing, more efficient viral vectors are being developed and promising new potential targets have been identified. For instance, recent research is focused on gene repair, in vivo, to treat heritable forms of HF, while strong experimental evidence indicates that specific microRNAs can be delivered to post-ischemic hearts to induce regeneration, a result that was previously thought possible only by using stem cell therapy. Gene therapy for HF is aging, but exciting perspectives are still very open.