Metabonomic Study of Amyotrophic Lateral Sclerosis in SOD1G93A Mouse Model

Abstract

Amyotrophic Lateral Sclerosis (ALS), the most common of the Motor Neuron Diseases (MND), is characterized by the progressive degeneration of the upper and lower motor neurons. Death ensues in 3-5 years from diagnosis which consists of scoring and a physical examination to rule out other motor disorders. Riluzole is the only drug approved so far and it offers only a modest 2-3 months of extension of life with little symptomatic relief. The search for an effective therapy is a daunting uphill task with numerous agents failing in clinical trials despite showing efficacy in the preclinical disease endpoints. Here we present a panel of metabolites covering some of the hallmark pathways of the disease, ranging from energy metabolism, to mitochondria health. Sharing common pathways and specific metabolites with a clinical metabonomic study, our study offers opportunity for the development of translatable approaches to measuring drug efficacy preclinically.