Gabisonia Khatia, Recchia Fabio A
Institute of Life Sciences, Fondazione Toscana Gabriele Monasterio, Scuola Superiore Sant'Anna, Piazza Martiri della Liberta` 33, 56127, Pisa, Italy.
Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Curr Heart Fail Rep. 2018 Dec;15(6):340-349. doi: 10.1007/s11897-018-0410-z.
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.
目前关于心力衰竭（HF）发生和发展的病理生理及分子机制的知识极为丰富。然而，实验结果与治疗选择之间的差距仍然很大，现有的药物治疗大多陈旧且疗效有限。多年前，为了寻找针对分子改变的新的非药物策略，研究人员提出了针对HF的基因治疗。在此，我们将回顾过去几年提出的一些针对导致严重心脏损伤发展为HF的主要致病机制/因素的策略，并论证继续开展该领域研究的必要性。
经过数十年的临床前研究以及热情与失望交织的阶段，近年来终于启动了临床试验。首个进入II期并测试肌浆网钙ATP酶基因递送的试验并未取得令人鼓舞的结果；然而，其他试验仍在进行中，更高效的病毒载体正在研发，并且已经确定了有前景的新潜在靶点。例如，最近的研究集中在体内基因修复以治疗遗传性HF形式，同时有力的实验证据表明，特定的微小RNA可以递送至缺血后心脏以诱导再生，而这一结果此前被认为只有通过干细胞治疗才有可能实现。HF的基因治疗虽已历经多年，但令人兴奋的前景依然广阔。
