DEVELOPING A NOVAL CARBON 13 TEST FOR MONITORING UREAGENESIS

该项目的目的是开发一种超灵敏的稳定器 同位素测试，将测量患者的尿路生成率 典型的(严重)鸟氨酸转氨酶缺乏症 (OTCD)形成尿素的速率是对照组的5% 人口。在这个节骨眼上，我们将尝试开发这样的测试 只有在健康的成年人中。 我们的基本假设是：a)我们可以成功地监测尿失禁 通过测量尿素中H13CO3的含量；b)质量 我们将为此使用的光谱方法将被证明是非常敏感的 以允许测定尿路形成，即使它是5% 控制值；c)OTCD受试者将在以下时间由H13CO3生成(13C)尿素 明显低于控制组的比率；d)拟议的 测试将是非常敏感的，它将允许我们甚至检测到非常小的 (5-10%)接受安慰剂治疗的OTCD患者尿失禁发生率的变化 含有OTC基因的cDNA的腺病毒载体。临床部 因此，该项目的意义将是开发一种 临床试验，我们可以用来监测基因治疗的疗效 这种先天的新陈代谢错误。

The purpose of this project is to develop an ultra-sensitive stable isotope test that will measure the rate of Ureagenesis in patients with the classical (severe) form of ornithine transcarbamylase deficiency (OTCD) who form urea at a rate that is <5% of that of the control population. At this juncture we will be attempting to develop such a test only in healthy adults. Our underlying hypotheses are: a) We can successfully monitor ureagenesis by measuring the incorporation of H13CO3 into urea; b) The mass spectrometric methods we will use for this purpose will prove so sensitive as to allow the determination of Ureagenesis even if it is <5% of the control value; c) subjects with OTCD will form (13C) urea from H13CO3 at a rate that is significantly less than that of controls; d) The proposed test will be so sensitive that it will permit us even to detect very small (5-10%) changes in the rate of ureagenesis in OTCD patients who receive an adenoviral vector containing a cDNA for the OTC gene. The clinical significance of this project, therefore, will be the development of a clinical test with which we can monitor the efficacy of gene therapy for this inborn error of metabolism.