NOVEL BREATH TEST TO DETERMINE MITOCHONDRIAL FUNCTION

肝脏疾病的管理受到严重阻碍，因为准确和 不存在灵敏的肝功能测量。肝病专家 普遍认为，目前的测试和方法不提供足够的 做出关于有效性的关键决策所需的信息 治疗或如何确定肝脏的最佳候选人 移植我们的目标是通过开发一个 试验，以确定肝损害的程度和进展， 不同原因的肝病患者。 在第一阶段，我们为实现目标迈出了第一步， 这证明了甲氧苄啶呼气试验（MBT）的潜力。的 MBT的新奇在于它是肝功能的特异性测量。 这是通过使用稳定同位素标记的底物13 C- 甲硫氨酸，其仅由肝线粒体代谢。当 C-甲硫氨酸被代谢，13 C 02的浓度增加， 呼气我们的研究表明，该测试是可重复的， 诱导的线粒体功能变化，并与标准 血清测试在第二阶段，我们将进行所需的验证研究， FDA的批准，以证明MBT的能力，提供预后 信息.该测试将是第一个FDA批准的产品 适应症 拟议的商业应用： 酒精相关性肝硬化和肝炎是一种肝脏疾病， 在美国，这是一个严重而广泛的问题。有一百万 终末期肝病患者和600万例病毒性肝炎。的MBT 将由医生用于确定肝脏的适当性 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.