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Novel Spectral Biomarkers for Alzheimer's Disease

阿尔茨海默病的新型光谱生物标志物

基本信息

批准号：
10359211
负责人：
Cynthia Therese McMurray
金额：
$ 21.03万
依托单位：
UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10359211
关键词：
Address Affect Alzheimer&apos s Disease Alzheimer&apos s disease patient Alzheimer&apos s disease therapy Alzheimer’s disease biomarker Animal Disease Models Animal Model Animals Biological Markers Cells Characteristics Chemicals Chemistry Classification Clinical Trials Complex Disease Electrons Environment Etiology Failure Fibroblasts Fingerprint Fourier Transform Frequencies Functional disorder Goals Human Impaired cognition Individual Inflammation Intervention Label Light Lipids Measures Memory Methods Mitochondria Modeling Molecular Molecular Profiling Movement Mus Mutation Neurofibrillary Tangles Onset of illness Oxygen Patients Pharmaceutical Preparations Pharmacotherapy Phenotype Physiological Process Proteins Recovery Reporting Sampling Technology Testing Therapeutic Tissues Treatment outcome base care costs cell type chemical bond chemical fingerprinting clinically relevant disease phenotype disease-causing mutation disorder control drug discovery effective therapy improved outcome mouse model mutational status novel novel therapeutics outcome prediction predictive marker prevent response synchrotron radiation therapeutically effective therapy outcome treatment response vibration

项目摘要

ABSTRACT. New therapies are urgently needed to treat AD patients, but we have no biomarker to determine when to start treatment and we lack approaches to predict the onset of disease and the outcome of therapeutics. The slow movement towards effective therapeutics brings us to a juncture at which longstanding approaches to drug discovery are no longer sufficient to identify successful therapeutics. New methods are needed if we are to improve the outcome of clinical trials or to develop more effective therapies. We have established a new platform for treating AD patients and new kind of biomarker to follow efficacy. The platform is XJB-5-131, a powerful electron scavenger which exerts its effects by targeting mitochondria (MT) directly and, among other effects, neutralizes oxygen damage and inflammation. The new biomarker is the spectral phenotype of the cell. Different from more conventional endpoints, we will used Fourier transform infrared light (FTIR) spectromicroscopy to follows changes in cell chemistry. The new biomarker method is powerful because cell chemistry changes in the disease state and in in response to drugs. FTIR is sensitive enough to detect both the disease state and drug effects. These findings arose from evaluating the effects of XJB-5-131 in HD animal models. In this proposal, we will apply the methods to AD animal models and in human AD fibroblasts. Animals with distinct mutational backgrounds will be tested for the timing and extent of their response using the FTIR biomarkers. AD fibroblasts with no known disease-causing mutation will be grouped according to the FTIR signature. We will test whether patients in the same FTIR class, i.e., the same chemistry, respond the same way to XJB-5-131. The goal is to develop an effective therapy and a new biomarker to evaluate when to start treatment and to predict the onset and outcome of treatment.

摘要。