CSF Indicators for Diagnosis and Disease Progression of ALS

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): In the United States, approximately 30,000 individuals have amyotrophic lateral sclerosis (ALS), with 5000 new cases being diagnosed each year. ALS is one of the most debilitating neurodegenerative diseases with an adult onset (30-70 years of age). It is clinically characterized by difficulties with speech and swallowing, muscle weakness, wasting, fesiculations and spasticity resulting from selective degeneration of cortical and spinal motorneurons. Death resulting from respiratory failure typically occurs within 3-5 years from diagnosis. Currently there is no treatment that significantly ameliorates or delays the progression of the disease. Furthermore, there is little to no understanding of the underlying pathophysiological processes of this disorder. Sporadic cases of ALS make up ~95% of the total cases and there is no specific lab test that can confirm the diagnosis. The gold standard continues to be clinical examination supported by lab testing that rules out conditions that may mimic ALS, but this is complicated by the highly variable presentation of the disease. Treatment of ALS is delayed because progression of disease is an important part of the clinical presentation and early cases of ALS are difficult to diagnose. Specific biologic markers for diseases such as lupus, paraneoplastic syndromes, and myasthenia gravis directly reflect the cause of these diseases and are the preferred diagnostic methods. This proposal outlines experiments to determine if similar biologic markers can be identified in ALS patients. Our preliminary data indicate that in ALS patient cerebral spinal fluid (CSF) there are antibodies to specific proteins in the central nervous system (CNS). Eight of ten patient samples examined so far had these antibodies. The antibodies were not present in healthy or neurological control samples tested. The question of autoimmunity in ALS remains controversial; however, antibodies to specific proteins in ALS patients would be of clinical and scientific value. The experiments in this proposal take advantage of unique clinical resources and are designed to further investigate if there are antibodies to specific CNS proteins present in ALS patients. If so, these antibodies may provide a clinical test that would allow for a more rapid diagnosis of the disease. Furthermore, if such antibodies are found, identification of the proteins to which these antibodies are directed may provide insight into disease pathology for at least a sub-population of sporadic ALS patients. This would help direct future research to identify effective therapeutic approaches. PUBLIC HEALTH RELEVANCE: The experiments in this proposal take advantage of unique clinical resources and are designed to further investigate if there are antibodies to specific CNS proteins present in ALS patients. If so, these antibodies may provide a clinical test that would allow for a more rapid diagnosis of the disease. Furthermore, if such antibodies are found, identification of the proteins to which these antibodies are directed may provide insight into disease pathology for at least a sub-population of sporadic ALS patients. This would help direct future research to identify effective therapeutic approaches.