Kits to Quantitate and Analyze Mitochondrial Proteins

定量和分析线粒体蛋白的试剂盒

• 批准号: 7191620
• 负责人: Michael F Marusich
• 金额: $ 37.49万
• 依托单位: MITOSCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-07 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7191620
• 关键词: Adverse effects; Agreement; Applied Research; Area; Basic Science; Biological Assay; Biological Markers; Cells; Characteristics; Clinical; Communities; Complex; Defect; Degenerative Disorder; Detection; Development; Development, Other; Diagnosis; Diagnostic; Diagnostic tests; Disease; Energy Metabolism; Enzymes; Feedback; Functional disorder; Generations; Goals; Grant; Hand; Inborn Genetic Diseases; Incentives; Individual; Inherited; Intellectual Property; Language; Legal patent; Licensing; Life; Marketing; Measurement; Measures; Medicine; Methods; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Monitor; Monoclonal Antibodies; Multienzyme Complexes; Non-Insulin-Dependent Diabetes Mellitus; Online Systems; Oregon; Parkinson Disease; Pathology; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Policies; Principal Investigator; Production; Proteins; Proteomics; Publications; Publishing; Range; Reagent; Relative (related person); Reporting; Research; Safety; Sales; Sampling; Scientist; Screening procedure; Small Business Technology Transfer Research; Stream; Structure; System; Technology; Testing; Therapeutic; Toxic Environmental Substances; Universities; Validation; Work; base; commercialization; design; drug development; enzyme activity; high throughput screening; human disease; innovation; mitochondrial dysfunction; molecular pathology; novel; novel therapeutics; prevent; prototype; response

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.

描述（由申请人提供）：线粒体功能障碍是许多疾病的病理基础，包括遗传性线粒体疾病、许多退行性疾病以及某些治疗药物的副作用。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检测试剂盒来满足这些需求，这些试剂盒可以简化关键线粒体蛋白的分析并增加强大的新分析功能。这些创新试剂盒基于首席研究员开发的一套独特的专有试剂和相关知识产权。这些试剂是单克隆抗体 (mAb)，可免疫捕获完整的功能性线粒体酶，其知识产权是涵盖这些 mAb 及其应用的专利（正在申请中）。第二阶段 STTR 拨款将推动这些技术在三个领域的商业化：1）药物细胞毒性安全筛选，以指导新药开发并监测许可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（致病性和诊断性）的应用研究。我们成功实现了第一阶段的目标，并积极完成了额外的工作。所有三种类型套件的工作原型均已在手，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试剂盒的早期版本，并已确定对它们有强烈的科学和商业需求。第二阶段工作将完成这些和其他测试的开发，并验证其技术实用性，为商业化做好准备。用通俗语言来说：线粒体是细胞的动力源，产生生命所需 95% 的能量。拟议的试剂盒将实现个性化线粒体医学，包括测量个体的线粒体毒性负荷（他/她的线粒体能量产生系统受损的程度），并允许评估个体对线粒体毒性药物的敏感性（包括治疗药物和药物的不良反应）。环境毒素）。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针对这些疾病的新疗法是否能提供有益的结果。最后，他们将提供一种新的治疗药物的方法，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。

项目成果

Lateral-flow immunoassay for detecting drug-induced inhibition of mitochondrial DNA replication and mtDNA-encoded protein synthesis.

用于检测药物诱导的线粒体 DNA 复制和 mtDNA 编码蛋白质合成抑制的侧流免疫分析。

• DOI: 10.1016/j.jim.2008.12.002
• 发表时间: 2009
• 期刊: Journal of immunological methods
• 影响因子: 2.2
• 作者: Nadanaciva,Sashi;Willis,JohnH;Barker,MelissaL;Gharaibeh,Dima;Capaldi,RoderickA;Marusich,MichaelF;Will,Yvonne
• 通讯作者: Will,Yvonne