Kits to Quantitate and Analyze Mitochondrial Proteins

描述（由申请人提供）：线粒体功能障碍是许多疾病病理学的基础，包括遗传性线粒体疾病、许多退行性疾病和某些治疗药物的不良反应。目前还没有可靠的标准化方法来检测和分析这些缺陷。我们的目标是通过一套新颖的分析试剂盒来满足这些需求，这些试剂盒简化了关键线粒体蛋白的分析，并增加了强大的新分析能力。这些创新的试剂盒是基于一套独特的专有试剂和相关的知识产权开发的主要研究人员。试剂是单克隆抗体（mab），免疫捕获完整，功能性线粒体酶，知识产权是专利（正在申请），涵盖这些单克隆抗体及其应用。第二阶段STTR拨款将在三个领域推动这些技术的商业化：1)有丝分裂毒性的药物安全性筛选，既指导新药开发，又监测已获许可的治疗药物的不良反应；2)通过简单的标准化测试诊断线粒体疾病（遗传性和获得性）；3)研究应用范围从线粒体结构/功能的基础研究，到有助于识别线粒体疾病生物标志物（致病和诊断）的应用研究。我们已经成功实现了第一阶段的目标，并主动完成了额外的工作。所有三种类型的工具包的工作原型都在手，我们已经记录了它们的基本性能特征。我们目前正在销售一些工具包的早期版本，并且已经确定对它们有很强的科学和商业需求。第二阶段的工作将完成这些和其他测试的开发，并验证其技术效用，为商业化做好准备。通俗地说：线粒体是细胞的发电站，产生生命所需能量的95%。拟议的试剂盒将实现个性化线粒体医学，包括测量个体的有丝分裂毒性负担（他/她的线粒体能量产生系统受损的程度），并允许评估个体对有丝分裂毒性药物的敏感性（包括治疗药物和环境毒素的不良影响）。该试剂盒还将用于检测和监测遗传性线粒体疾病和退行性疾病（如帕金森病和2型糖尿病）的进展，这将帮助临床医生确定这些疾病的新疗法是否能带来有益的结果。最后，他们将为新的治疗药物提供一种方法，可以保护线粒体免受有毒物质的侵害，从而有可能预防或治疗线粒体疾病。

DESCRIPTION (provided by applicant): Mitochondrial dysfunction underlies the pathology of many disorders, including inherited mitochondrial diseases, many degenerative diseases, and the adverse effects of certain therapeutic drugs. At present there are no reliable standardized methods for detection and analysis of these defects. Our goal is to meet these needs with a set of novel assay kits that simplify analysis of key mitochondrial proteins and add powerful new analytical capabilities. These innovative kits are based on a unique set of proprietary reagents and associated intellectual properties developed by the Principal Investigators. The reagents are monoclonal antibodies (mAbs) that immunocapture intact, functional mitochondrial enzymes, and the intellectual properties are patents (pending) that cover these mAbs and their application. The Phase II STTR grant will drive commercialization of these technologies in three areas: 1) pharmaceutical drug safety screening for mitotoxicity, both to guide new drug development and to monitor adverse effects of licensed therapeutic drugs; 2) diagnosis of mitochondrial disorders (inherited and acquired) with simple standardized tests; and 3) research applications ranging from basic research into mitochondrial structure/function, to applied research that will help identify biomarkers (pathogenic and diagnostic) of mitochondrial disease. We have successfully met our Phase I goals and also accomplished additional work proactively. Working prototypes of all three types of kits are in hand and we have documented their basic performance characteristics. We are currently marketing early versions of some kits, and have established that there is a strong scientific and commercial demand for them. Phase II work will complete the development of these and other tests and validate their technical utility, making them ready for commercialization. Relevance in lay language: Mitochondria are/the powerhouse of cells and produce 95% of the energy needed for life. The proposed kits will enable personalized mitochondrial medicine, including measurement of an individual's mitotoxic burden (the degree to which his/her mitochondrial energy production system is damaged), and allow assessment of an individual's sensitivity to mitotoxic agents (including adverse effects of therapeutic drugs and environmental toxins). The kits will also be used to detect and monitor the progression of inherited mitochondrial diseases and degenerative diseases such as Parkinson's and Type-2 diabetes, and this will help clinicians determine whether or not new therapies for these disorders provide beneficial results. Finally, they will offer a way to for new therapeutic drugs that can protect mitochondria from toxic agents, and thus potentially prevent or treat mitochondrial disorders.