The long-term goal of this research program is to discover protein biomarkers for Amyotrophic Lateral Sclerosis (ALS). Biomarkers for neurodegenerative diseases are necessary for accurate diagnosis and monitoring of disease progression and response to therapy. Biomarkers also provide important clues about mechanisms of disease pathogenesis, identifying pathways of cellular dysfunction during the course of disease. Success in biomarker discovery is greatly enhanced when investigation is focused on a homogenous disease population where there is a relevant animal model of the disease. ALS caused by mutations in superoxide dismutase 1 (SOD1-ALS) meets these criteria, and is the focus of this proposal. There are two specific aims: 1) We will use state of the art proteomic methods to quantitatively compare 3000 proteins from spinal cords and motor nerves of SOD1-ALS mice and their normal littermates. We will compare mice from presymptomatic, early symptomatic and late stages of disease in order to correlate protein patterns with the progression of disease. 2) We will select a subset of proteins (about 40) as possible candidate biomarkers based on rank order criteria, such as magnitude of change and progression of change with disease. In order to translate the proteomic findings from tissues into biomarkers that might be used in clinical practice, the selected proteins will be specifically investigated in plasma and spinal fluid samples from SOD1-ALS mice and controls. Finally, we will investigate these candidate biomarkers in plasma and spinal fluid samples from people with ALS, including those with SOD1-ALS and those with sporadic ALS. Here we will take advantage of the large clinical research database of families with ALS at the Emory ALS Center. This proposal represents a systematic approach to biomarker discovery using the most modern technology available combined with sophisticated bioinformatics. We will use these tools develop biomarkers for ALS that are essential for identifying pathogenic mechanisms and developing novel treatments. We propose to use state of the art proteomics combined with sophisticated bioinformatics to identify protein biomarkers in Amyotrophic Lateral Sclerosis (ALS). We will screen for changes in about 3000 proteins in spinal cord and nerve tissue from the SOD1-ALS mouse, and then identify a specific subset of proteins as potential biomarkers. These candidate biomarkers will be tested for their sensitivity and specificity for disease in plasma and spinal fluid samples from mice and people with ALS. ? ? ?
| Choksi, Dipti; Idnani, Barkha (2013) A RESEARCH REVIEW ARTICLE ON COMPOSITE MATERIAL. Asian academic research journal of multidisciplinary 1:44-56 |
| Zhou, Jian-Ying; Afjehi-Sadat, Leila; Asress, Seneshaw et al. (2010) Galectin-3 is a candidate biomarker for amyotrophic lateral sclerosis: discovery by a proteomics approach. J Proteome Res 9:5133-41 |
