<International Circulation>: Have you found any of these targets?
　　《国际循环》：您有没有发现这些靶位?
　　Dr. Koch: We published a paper last year on one of the non-GCPR targets of this kinase. It turns out to be to the insulin receptor substrate 1 (IRS1). GRK2 negatively impacts insulin signaling. This may or may not be related to pro-death， but because we found an unusual target for GRK2， we are now looking in the mitochondria. GRK2 is in mitochondria， we do not entirely understand its mechanisms， but it is certainly the mitochondrial cell-death paths that are worth more research.
　　Koch博士: 去年我们发表了一篇有关这个激酶的non-GCPR靶位的论文。原来它是胰岛素受体基质1(IRS1)。GRK2对胰岛素信号产生负面影响。这与死亡预警也许有关，也许无关， 但是我们却因此发现了在线粒体中GRK2的不寻常靶位。我们并不完全了解GRK2在线粒体中作用机制， 但是线粒体细胞死亡路径肯定值得我们做更多的研究。
　　<International Circulation>: Could you please give us a brief explanation of the GRK targets in pre-clinical studies as a method of HF intervention?
　　《国际循环》：您能否给我们简短的说明一下在临床前研究中如何将GRK靶位作为一个调控心力衰竭的方法?
　　Dr. Koch: We are attempting gene therapy. The best way we know to inhibit GRK2 in-vivo is with a peptide that we developed called the bARK (Beta adrenergic?receptor?kinase) CT. We have done a large-animal， pre-clinical study were we have reversed HF in a pig model. We are working with the FDA， within an NIH sponsorship， to perform a phase I clinical trial. All that is needed is a larger animal toxicity study. Over the last decade， I have worked with companies to develop small-molecule inhibitors. Not all of those programs have been successful. Our latest research that shows paroxetine (paxil) as a GRK2 inhibitor will spur other new companies to get involved and find new small-molecule inhibitors.
　　Koch博士:我们正在尝试基因疗法。我们知道在体内抑制GRK2的最好的方法是用我们开发的一种叫做bARK (β肾上腺素受体激酶)CT的缩氨酸。我们已经做了大量的动物和临床前研究，在猪的动物模型中已经成功逆转了心力衰竭。我们正在与美国食品药物管理局（FDA）内部的一个国家卫生研究院（NIH）合作进行第一阶段的临床试验。这一试验的全部工作就是需要做一个更大的动物毒性试验。在过去的十年里，我曾与公司开发小分子抑制剂。并不是所有的项目都是成功的。我们的最新研究表明帕罗西汀(paxil)作为可以作为GRK2的抑制剂，这一结果将激励更多的新公司参与进来，共同寻找新的小分子抑制剂。
　　<International Circulation>:Do anticipate paroxetine going to full trials?
　　《国际循环》：您期望对帕罗西汀进行全面的实验吗?
　　Dr. Koch: With the bARK CT， yes. We will go to phase one clinical trial. There is already one gene therapy for heart failure that has completed phase I and II with a different gene. The safety adeno-associated vectors is there. The phase I study will be in about two dozen， sick， end-stage heart failure patients. We will move on from there.
　　Koch博士: 是的，和bARK CT一起。我们将进行第一阶段的临床试验。现在已经有了一个治疗心力衰竭的基因疗法， 并且已经利用不同的基因完成临床一期和二期实验。我们已经有了安全的腺病毒-关联载体。第一阶段的研究将在大约24名， 患病， 晚期心力衰竭患者中进行。我们将在此基础上继续前行。

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