Serum Proteomics for Biomarker Discovery in Batten Disease

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Identification of biomarkers for neurodegeneration and for progression of neurodegeneration would be important for diagnosis, for following clinical progression of disease and, most importantly, for identification of, and monitoring efficiency of treatments. We propose to systematically characterize blood serum markers in a well defined genetically inherited neurodegenerative disease. The juvenile neuronal ceroid lipofuscinoses (JNCL or Batten disease) is a lysosomal storage disorder that represents one of the most common groups of neurodegenerative diseases of childhood. Clinical manifestations that include progressive blindness, decline in cognitive function, seizures, and motor dysfunction culminating in premature death. The objective of this proposal is to identify candidate protein biomarkers in serum of NCL patients, and more specifically in the juvenile subtype (JNCL or Batten disease), and develop a panel of disease biomarkers that can aid in assessing disease progression and possible diagnosis of this disorder. We have serum samples from 60 patients with genetic confirmation of JNCL at various ages, and state of disease progression. In addition, we have serum samples from a cohort of patients drawn over a period of 5 years that will allow for comparative analysis. A sub-set of these samples include serum taken at a pre-symptomatic time point. In addition, through the Batten Disease Diagnostic and Clinical Research Center we have clinical profiles in the form of the Unified Batten Disease Rating Scale on patients whose serum will be used for this study. We propose two aims: (i) An exploratory characterization of the protein species present in blood serum from JNCL patients and unaffected subjects will be performed using two-dimensional gel electrophoresis (2DGE) to identify differentially expressed proteins. (ii) Profiling of the leukocyte proteome by 2DGE may reveal the activation and expression of specific inflammatory response related proteins that can be used as disease biomarkers and potential indicators of disease progression. As our understanding of the neurodegenerative pathways in the NCLs increases, it is beginning to become apparent that the NCL disorders may also share some common pathological features with other, more common, neurodegenerative diseases such as Alzheimer's and Parkinson's. Thus our studies have the potential to broadly impact other neurodegenerative diseases and has wide ranging significance to CNS disease. Completion of the proposed studies would likely prove valuable in identification of markers of more complex neurodegenerative diseases