NOVEL BREATH TEST TO DETERMINE MITOCHONDRIAL FUNCTION

肝病的管理受到严重阻碍，因为准确和 目前尚不存在衡量肝功能的敏感指标。肝病专家 普遍认为，目前的测试和方法不能提供足够的 做出有关疗效的关键决策所需的信息 治疗或如何确定肝脏的最佳候选者 移植。我们的目标是通过开发一种 测试以确定肝脏损害的程度和进展 有不同原因的肝病患者。 在第一阶段，我们迈出了实现目标的第一步，方法是 展示蛋氨酸呼气试验(MBT)的潜力。这个 MBT的新奇之处在于它是肝功能的一种特殊衡量标准。 这是通过使用稳定的同位素标记底物13C-来实现的。 蛋氨酸，它只由肝脏线粒体代谢。什么时候 C-蛋氨酸被代谢，13C02浓度增加 呼吸急促。我们的研究表明，这项测试是可重复性的，对 线粒体功能的改变，并与标准 血清检测。在第二阶段，我们会进行所需的验证研究 FDA的批准，以证明MBT提供预后的能力 信息。这项测试将是FDA批准的第一种产品 指示。 建议的商业应用： 与酒精相关的肝硬变和肝炎是一种 在美国存在严重而广泛的问题。有一百万人 终末期肝病患者和600万病毒性肝炎患者。MBT 将被内科医生用来确定肝脏的适宜性 移植，连续跟踪疾病进展，并评估 药物治疗的好处。

The management of liver disease is severely hampered because accurate and sensitive measures of liver function do not exist. Hepatologists universally agree that current tests and methods do not provide enough information necessary to make critical decisions about efficacy of treatment or how to identify the best candidates for liver transplantation. Our objective is to address this need by developing a test to determine the degree and progression of liver impairment in patients with varying causes of liver disease. In Phase I, we took the first step in achieving our objective by demonstrating the potential of the Methionine Breath Test (MBT). The novelty of the MBT is that it is a specific measure of liver function. This is achieved by using the stable isotope labeled substrate, 13C- methionine, which is metabolized exclusively by hepatic mitochondria. When C-methionine is metabolized, the concentration of 13C02 increases in expired breath. Our studies show the test is reproducible, responds to changes induced in mitochondrial function, and correlates with standard serum tests. In Phase II, we will conduct the validation studies required for FDA clearance to demonstrate the MBT's ability to provide prognostic information. The test will be the first FDA approved product for this indication. Proposed commercial applications: Liver disease in the form of alcohol related cirrhosis and hepatitis is a serious and extensive problem in the United States. There are 1 million end stage liver patients and 6 million cases of viral hepatitis. The MBT will be used by physicians to determine appropriateness of liver transplantation, serially follow the disease progression, and evaluate the benefit of drug therapies.