Development of an Alzheimer's disease specific antibody biomarker for a tau oligomer fragment

开发 tau 寡聚体片段的阿尔茨海默病特异性抗体生物标志物

• 批准号: 9409478
• 负责人: JAMES G. MOE
• 金额: $ 30.21万
• 依托单位: OLIGOMERIX, INC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9409478
• 关键词: Alzheimer disease detection; Alzheimer' s Disease; Antibodies; Biological; Biological Assay; Biological Markers; Biological Sciences; Blood; Brain; Brain Diseases; Businesses; Cerebrospinal Fluid; Cleaved cell; Clinical; Collaborations; Competence; Cost of Illness; Development; Diagnostic; Diagnostic tests; Direct Costs; Disease; Disease Progression; Employee Strikes; Ensure; Enzyme-Linked Immunosorbent Assay; Epitopes; Goals; Hybridomas; Immunoblotting; Immunohistochemistry; Immunotherapeutic agent; Impairment; Laboratories; Legal patent; Liquid substance; Memory Loss; Methods; N-terminal; Pathologic; Pathology; Patient Recruitments; Patients; Pattern; Peptides; Pharmaceutical Preparations; Phase; Plasma; Prevalence; Production; Proteins; Recombinants; Reproducibility; Research; Role; Signal Transduction; Site; Small Business Innovation Research Grant; Specificity; Specimen; Staging; Structure; Surrogate Markers; Therapeutic; Therapeutic Studies; Therapeutic Uses; aging population; assay development; base; blood-based biomarker; brain tissue; commercialization; cost; drug development; drug discovery; early detection biomarkers; effective therapy; experience; extracellular; in vivo; loss of function; minimally invasive; noninvasive diagnosis; notch protein; novel; phase 1 study; polyclonal antibody; prevent; programs; small molecule therapeutics; success; synaptic function; tau Proteins; tau aggregation

PROJECT SUMMARY - Phase I SBIR (PA-16-302) Title - Development of an Alzheimer’s disease specific antibody biomarker for a tau oligomer fragment The prevalence of Alzheimer’s disease (AD) is increasing worldwide due to demographic shifts and an aging population and currently there are no disease-modifying drugs. It is the most costly disease in the US with a financial burden of over $236 billion annually in direct costs that is estimated to increase to $1 trillion by 2050. There is an urgent unmet need for the development of blood biomarkers for the early detection and staging of AD. The lack of accurate, sensitive, and well-validated biomarkers for AD is a rate limiting factor for identifying effective treatments. Tau protein, and in particular tau oligomers, have become a high priority target for AD due to 1) their high correlation with diseased regions within the brain of AD patients, 2) their newly discovered extracellular activity that is believed to result in the impairment of synaptic function and loss of memory and 3) their role in the spread of pathology. Oligomerix has developed novel methods to highly purify tau oligomers and has discovered that they undergo autoproteolytic fragmentation at specific sites creating neo-epitopes at the cut ends. Polyclonal antibodies (pAbs) to the neo-epitopes were generated, and one pAb showed a striking specificity for AD specimens. In Aims 1 and 2, monoclonal Abs (mAbs) will be generated that have specificity for this fragment end and specificity for the uncut site. Aim 3 will be to characterize the mAbs and perform a proof-of-concept biomarker study. The overall goal of this project is to produce a blood-based, non-invasive diagnostic test as a biomarker for tau fragment levels from biological specimens for AD. These mAbs can also be used to understand the role of tau autoproteolytic fragmentation in AD, and the ratio of cut to uncut tau at this site may provide greater sensitivity in determining AD stage. Additionally, the tau fragment specific mAb that will be developed under the proposed program could have tremendous commercial utility for any therapeutic program, immuno- or small molecule therapeutics seeking to reduce tau accumulation, enhance clearance, or prevent the formation of tau oligomers. The global CNS biomarker market is projected to reach $5.1 billion by 2020 from $3.1 billion in 2015. The proposed study will be enabling for Oligomerix’s internal drug discovery programs, and the Company will make these assays available by commercializing them via collaboration with a diagnostic or life sciences company. Thus the proposed program, if successful, will have significant commercial potential and impact. The strong management and scientific team will ensure competencies in mAb production and characterization, as well as assay development and commercialization. Furthermore, the presence of Dr. Peter Davies and Dr. Steven Jacobsen on the Scientific Advisory Board provide top notch scientific and business experience to the Company.

项目摘要-第一期SBIR （PA-16-302）