Lefty - a novel anti-fibrotic molecule for the treatment of kidney disease

患有进行性肾脏疾病的患者会发展为终末期肾衰竭，这需要透析或器官移植的强化医疗支持。这在澳大利亚和西方世界越来越普遍。这对个人来说是毁灭性的，它给我们的医疗体系带来了巨大的经济压力。此外，肾功能衰竭是心血管疾病的一个强大而独立的危险因素。目前的治疗最多只能减缓肾脏疾病的进展速度，但不能阻止肾衰竭的持续发展。因此，有一个重大的医疗需要能够阻止，并希望扭转，这种无情的疾病。肾脏瘢痕形成（称为纤维化）是导致终末期肾衰竭的常见最终途径，与潜在肾脏疾病的性质无关。我们的初步研究表明，在细胞培养和动物研究中，一种叫做Lefty的天然蛋白可以抑制肾纤维化。这些非常有希望的结果导致了一种假设，即Lefty可以阻止，甚至逆转进行性肾脏疾病中肾脏的疤痕形成。我们将通过在肾纤维化动物模型中使用Lefty作为治疗方法来验证这一假设。进一步的细胞培养研究也计划检验Lefty调节肾纤维化的机制。如果成功，这些研究将为支持Lefty作为进行性肾脏疾病患者的临床治疗提供关键数据。

Patients with progressive forms of kidney disease go on to develop end-stage renal failure which requires intensive medical support of dialysis or organ transplantation. This is an increasingly common condition in Australia, and the Western world in general. It is devastating for the individual and it places an enormous economic strain upon our healthcare system. In addition, renal failure is a strong and independent risk factor for cardiovascular disease. Current treatments can at best slow the rate of progression of kidney disease, but cannot prevent the relentless progression to end-stage renal failure. Thus, there is a major medical need to be able to halt, and hopefully reverse, this relentless disease. Scarring of the kidney (termed fibrosis) is the common final pathway leading to end-stage renal failure regardless of the nature of the underlying kidney disease. Our preliminary studies have shown that a naturally occurring protein called Lefty can act to inhibit renal fibrosis in cell culture and animal studies. These very promising results have lead to the hypothesis that Lefty can halt, and perhaps even reverse, scarring of the kidney in progressive kidney disease. We will test this hypothesis by using Lefty as a treatment in animal models of renal fibrosis. Further cell culture studies are also planned to examine the mechanisms by which Lefty modulates renal fibrosis. If successful, these studies will provide critical data to support the development of Lefty as a clinical treatment for patients with progressive forms of kidney disease.