Transdermal Test for Active Tuberculosis

描述（由申请人提供）：本提案旨在建立一个 开发计划，将实验性透皮结核皮肤 测试成商业产品。这项技术已经证明了 特异性识别AFB+ TB患者的显著能力， 将少量TB蛋白（MPB 64）注射到皮肤上， 过敏性皮肤反应。PPD+无菌个体对 蛋白 MPB-64透皮贴剂应用于62名患者，其中49名 结核阳性活动性疾病和13人完成结核化疗， 非结核病但结核菌素阳性的对照。在72 h时读取结果。的 透皮贴剂的敏感性为87.8%，有效率为92.9%， 和百分之百的特异性。13名结核病患者每人完成了6项 3个月的结核病化疗显示出对MPB 64斑贴试验的不同反应： 在检测前完成化疗不到4个月的患者呈阳性; 5个月前完成化疗的患者中有50%呈阳性; 化疗前7个月和8个月完成者均为阴性。 所有结核菌素试验阳性的非结核病对照者， MPB-64透皮贴剂，即使在测试的最高蛋白剂量下。本测试 可能是区分活动性结核病患者和结核病感染者的有用方法， 无症状个体。 该技术的当前版本是研究级补丁。这项建议 将概述一个发展途径，以改善产品包装，易用性 和产品稳定性。最初的努力将是描述一种独特的动物 用于检查组件材料和技术的模型。我们的具体 目标是1。建立动物模型以测试制剂中的变量， 皮肤测试抗原的透皮递送，2.建立最大成本 MPB 64的有效来源，3.建立最佳包装/交付 技术的补丁，4。建立动物毒性试验程序， 产品发布和测试产品稳定性。第二阶段的目标包括优化 蛋白质生产和制造规模扩大，以及临床 进行产品注册试验。 拟定商业应用： 拟议的商业应用将是开发用于诊断筛查的斑贴试验 通过使用MPB 64蛋白的透皮递送，治疗活动性结核病例。 贴片 测试可以用来代替其他筛选测试，如PPD皮肤试验或AFB 涂片，作为诊断活动性结核病患者的一种手段。

DESCRIPTION (provided by applicant):This proposal seeks to establish a development program to transition an experimental Transdermal Tuberculosis Skin Test into a commercial product. This technology has already demonstrated a remarkable ability to specifically identify AFB+ TB patients by adminstering a small amount of a TB protein (MPB64) to the skin and monitoring for an erythemic skin response. PPD+ symptomless individuals are non-reactive to the protein. The MPB-64 Transdermal Patch was applied to sixty-two patients, 49 with sputum-positive active disease and 13 who had completed TB chemotherapy, and 28 non-TB but tuberculin-positive controls. The results were read at 72h. The sensitivity of the Transdermal Patch was 87.8 percent, efficacy 92.9 percent, and specificity 100 percent. The thirteen TB patients who had each completed 6 months of TB chemotherapy showed different reactions to MPB64 patch test: those who had completed chemotherapy less than 4 months before testing were positive; 50 percent of patients who completed chemotherapy 5 months prior were positive; and those who had completed chemotherapy 7 and 8 months before were negative. All the non-TB controls with positive tuberculin tests were negative to the MPB-64 Transdermal Patch, even at the highest protein dose tested. This test may be a useful method to distinguish active TB patients from TB-infected but asymptomatic individuals. The current version of the technology is a research grade patch. This proposal will outline a development pathway to improve product packaging, ease of use and product stability. Initial efforts will be to characterize a unique animal model for use in examining component materials and technologies. Our specific aims are 1. Validate an animal model to test variables in the formulation and transdermal delivery of the skin test antigen, 2. Establish the most cost effective source of MPB64, 3. Establish the best packaging / delivery technology for the patch, 4. Establish animal test procedures for toxicity, product release and to test product stability. Phase II aims include optimizing protein production and manufacturing scale up, and performance of clinical trials for product registration. PROPOSED COMMERCIAL APPLICATION: The proposed commercial application would be to develop a patch test for diagnostic screening of active cases of tuberculosis by using transdermal delivery of MPB64 protein. The patch test could be used in place of other screening tests, such as the PPD skin test or the AFB smear, as a means of diagnosing patients with active tuberculosis.