%0 Journal Article
%T Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach
%A Alok Kumar
%A Devlina Ghosh
%A R. L. Singh
%J Journal of Biomarkers
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/538765
%X Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3¨C5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients. 1. Introduction Motor neuron diseases (MND) are a heterogeneous group of disorders which result in death of motor neurons. These diseases may give rise to characteristic perturbations of the metabolome. Amyotrophic lateral sclerosis (ALS) is the most common form of MND in adults, affecting both anterior horn cells and corticospinal tracts. ¡°Amyotrophic¡± refers to the muscle atrophy, weakness, and fasciculation that signify disease of the motor neurons. The median age of ALS onset is 55 years. Fifty percent of patients die within three years of onset of symptoms, and 90% die within five years [1]. The incidence of ALS is from approximately 2 per 100,000 per year [2] and may be increasing [3]. The lifetime risk of ALS is 1 in 600 to 1 in 1000. The majority of ALS cases which have been reported are sporadic (SALS); 10% are familial (FALS), some of which arise from mutations in superoxide dismutase-1 (SOD1) [4], TAR DNA-binding protein (TDP43) [5, 6] and fused in sarcoma/translated in liposarcoma (FUS/TLS) [7, 8], ALS2 [9, 10], dynactin [11], and senataxin [12]. Genomic studies suggest the existence of at least eleven additional loci for FALS, but the genetic defects remain to be identified [13]. Using a genome-wide association study (GWAs) approach, it has been recently reported that a locus on chromosome 9p21 accounted for 40% of familial ALS and nearly 1 fourth of all ALS cases in a sample of 405 Finnish patients [14]. This association signal had previously been reported by van Es et al. [15] as related to ALS, and a meta-analysis amongst many studies showed that this was indeed the major signal for this disease [16]. Similarly, recent GWAs for
%U http://www.hindawi.com/journals/jbm/2013/538765/