Development of recombinant Lecithin Cholesterol Acyltransferase as a therapeutic

在过去的一年中，我们完成了重组LCAT（rLCAT）I期临床试验的样本分析，该试验于2012年秋季完成。 该研究在NIH进行，是一项在18名受试者中进行的单次剂量递增研究。 没有显著的不良事件，并且重组LCAT在其增加HDL水平的能力方面表现得与基于动物研究的预期一样。我们还批准了一个单一患者IND，用于用rLCAT治疗家族性LCAT缺乏症（FLD）患者。 rLCAT治疗使胆固醇酯水平恢复至接近正常水平，并高于防止LpX形成所需的阈值，LpX是在FLD中积累并导致肾脏疾病的异常脂蛋白颗粒。 rLCAT治疗还纠正了这种疾病中的其他脂蛋白异常，如低HDL，这可能会导致心血管疾病。

In the past year, we completed the analysis of samples from a Phase I clinical trial of recombinant LCAT (rLCAT), which we completed in the fall of 2012. The study was done at the NIH and was a single dose escalation study in 18 subjects. There was no significant adverse events and the the recombinant LCAT behaved like expected based on animal studies in regard to its ability to increase HDL levels. We were also granted approval for a single patient IND for the treatment of a patient with Familial LCAT Deficiency (FLD) with rLCAT. The rLCAT treatment restored cholesteryl ester levels to near normal levels and above threshold necessary to prevent LpX formation, the abnormal lipoprotein particle that accumulates in FLD and causes renal disease. The rLCAT treatment also corrected the other lipoprotein abnormalities in this disorder, such as low HDL, which may contribute to cardiovascular disease.