权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Signatures of Amyotrophic Lateral Sclerosis in Skeletal Muscle

骨骼肌肌萎缩侧索硬化症的分子特征

基本信息

批准号：
8619114
负责人：
PETER H KING
金额：
$ 22.04万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8619114
关键词：
Affect Amyotrophic Lateral Sclerosis Archives Atrophic Biological Markers Biopsy Specimen Cessation of life Clinic Clinical Clinical Research Clinical Trials Consensus Data Degenerative Disorder Detection Diagnosis Disease Disease Management Disease Progression Early Diagnosis Educational workshop Enrollment Fiber Funding Gene Expression Profile Goals Histology Intervention Laboratories Messenger RNA Molecular Molecular Profiling Molecular Target Monitor Motor Neurons Mus Muscle Muscle Weakness Neurodegenerative Disorders Neuromuscular Diseases Neuromuscular Junction Organ Paralysed Patients Pattern Pharmaceutical Preparations Phase Positioning Attribute Process Protein Isoforms Proteins Research Personnel Sampling Sequence Analysis Skeletal Muscle Specificity Staging Testing Time Tissues Treatment Efficacy Variant Work base clinical Diagnosis cohort deep sequencing disease diagnosis disorder control effective therapy improved mitochondrial dysfunction mouse model neuromuscular next generation novel novel therapeutics patient population pre-clinical protein expression public health relevance tool

项目摘要

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons that inexorably leads to progressive weakness and death. There is no specific biomarker for this disease, and the diagnosis is often delayed as clinical and electrophysiological examinations are often inconclusive in the early stages. Furthermore, once a diagnosis is estabished, the current tools to track patients are insensitive for the timely detection of disease improvement or worsening. A biomarker that can facilitate diagnosis, track disease progression, or both, would fill a large clinical gap in ALS management, and expedite clinical trials of novel therapies. The long term goal of this proposal is to identify molecular signatures in muscle of ALS patients that can serve as disease biomarkers. In ALS, changes occur in skeletal muscle prior to motor neuron death and clinical onset, such as structural changes in the neuromuscular junction, muscle restricted mitochondrial dysfunction, and fiber atrophy. Muscle is the "end organ" affected by the degenerative process of ALS and is the most accessible for molecular study. Here we hypothesize that gene expression patterns in muscle from patients with ALS contain molecular signatures that can serve as biomarkers of the disease. This hypothesis is based on preliminary data we obtained using next generation deep sequencing on muscle samples of clinically well characterized ALS patients. Using non-ALS disease- and normal control samples, we identified over 300 unique targets in ALS samples, including isoform variances, that will serve as the basis of study for this proposal. We are well positioned to carry out this study because of the large neuromuscular patient population, including ALS and ALS mimics, and our oversight of the electrodiagnostic and muscle histology laboratories. Here, we will further investigate our molecular targets with the following two specific aims: Specific Aims: 1. To validate ALS-specific targets and isoform variances identified by deep sequencing by performing PCR analysis of a large cohort of ALS and non-ALS muscle samples. 2: To assess protein expression of validated targets in muscle tissues from ALS patients and correlate targets with muscle samples from the G93A SOD1 ALS mouse.

肌萎缩性侧索硬化症（ALS）是一种运动神经元的退行性疾病，不可避免地导致