Developing a Diagnostic Blood Test for Sarcoidosis

描述(申请人提供)：结节病诊断检测有限责任公司是一家医疗诊断公司，开发一种结节病的诊断血液测试。结节病是一种多系统肉芽肿性疾病，在美国每年每10万人中约有10-40人患病，其中非洲裔美国人和女性影响不成比例。结节病可导致晚期肺纤维化、肺高压、心力衰竭、心脏性猝死和毁灭性的神经疾病。因此，结节病是一个重大的健康问题和健康差距问题。由于结节病可影响任何或多个器官，结节病必须与许多其他炎症性、感染性或免疫性疾病和癌症相鉴别。医学界的共识是，没有有用的血液测试或其他简单的方法来诊断结节病；诊断需要活检确认，通常是通过肺部或淋巴结活检，这伴随着风险和成本。诊断结节病的费用尚未公布，但估计每年可能超过2.25亿美元。显然，需要一种更安全、更具成本效益的结节病诊断血液检测方法。这一第一阶段的应用程序建议继续开发一种有前景的结节病诊断血液测试，最初是由约翰·霍普金斯大学高级诊断和实验治疗中心第一阶段(CADET I)奖资助开发的。这种诊断血液测试是基于发现一种特定的微生物蛋白--分枝杆菌过氧化氢酶-过氧化物酶(MKatG)，它能刺激大多数结节病患者的免疫系统。这项测试使用mKatG和其他微生物蛋白来刺激血液细胞释放炎性化学物质干扰素-γ来预测结节病。到目前为止，我们建议的血液检测的敏感性为65%，特异性为96%，阳性预测值为94%。有了这些有希望的结果，我们建议通过优化结节病不同亚组的测试特征来进一步发展这项测试，并建立这项测试的实验室程序的可靠性和操作范围。在这个第一阶段的提案中，我们还将开发一个商业原型诊断试剂盒，以测试在不同地理中心部署测试的可行性。最后，我们将与FDA建立上市批准程序，并完成预期多中心研究的框架，以验证该测试作为第二阶段申请的一部分。如果在第二阶段研究中成功验证，该测试可能会对临床医生诊断结节病的方式产生革命性影响，因为缺乏替代的安全和经济有效的测试。这样的测试将具有很高的商业应用潜力，如果广泛使用，可能会为美国医疗体系节省大量成本。

DESCRIPTION (provided by applicant): SARCOIDOSIS DIAGNOSTIC TESTING LLC is a medical diagnostics company developing a diagnostic blood test for sarcoidosis. Sarcoidosis is a multisystem granulomatous disorder that affects ~10-40 per 100,000 people per year in the U.S. and disproportionately affects African-Americans and women. Sarcoidosis can lead to advanced pulmonary fibrosis, pulmonary hypertension, heart failure, sudden cardiac death and devastating neurologic disease. Thus, sarcoidosis represents a significant health problem and health disparity concern. Because sarcoidosis can affect any or multiple organs, sarcoidosis must be differentiated from many other inflammatory, infectious or immunologic diseases and cancer. A consensus in the medical community is that there is no useful blood test or other easy way to diagnose sarcoidosis; a diagnosis requires biopsy confirmation, often by lung or lymph node biopsy, with its attendant risks and costs. The costs involved with diagnosing sarcoidosis have not been published, but estimates could exceed $225 million each year. The need for a safer, cost-effective diagnostic blood test for sarcoidosis is clear. This Phase I application proposes to continue the development of a promising diagnostic blood test for sarcoidosis initially developed with funding from a Centers for Advanced Diagnostics and Experimental Therapeutics in Lung Diseases Stage I (CADET I) award to Johns Hopkins University. This diagnostic blood test is based on the discovery of a specific microbial protein, mycobacterial catalase-peroxidase (mKatG) that stimulates the immune system in most patients with sarcoidosis. This test uses mKatG and other microbial proteins to stimulate release of the inflammatory chemical interferon-γ from blood cells to predict sarcoidosis. To date, our proposed blood test has a sensitivity of 65%, a specificity of 96% and a positive predictive value of 94%. With these promising results, we propose to further develop this test by optimizing test characteristics for different subgroups with sarcoidosis and to establish the reliability and operating range of laboratory procedures for this test. In this Phase I proposal, we will also develop a commercial prototype diagnostic kit to test the feasibility of deploying the test in different geographic centers. Finally, we will establish a marketing approval process with the FDA and complete a framework for a prospective multicenter study to validate this test as part of a Phase II application. If successfully validated in Phase II studies, the test could have a transformative impact on how clinicians diagnose sarcoidosis given the absence of an alternative safe and cost-effective test. Such a test would have a high potential for commercial application and with widespread use could result in considerable cost savings to the U.S. healthcare system.