Biomarker for amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a disabling and fatal neurodegenerative motor neuron disease whose unresolved etiology is likely to be multifactorial involving both environmental and genetic factors. Neither risk factors (increasing the likelihood of disease initiation or promotion) have been unambiguously elucidated nor reliable diagnostic markers (complying with sensitivity and specificity requirements) have been validated or even clinically proven. Beyond that, no efficient therapy or pharmacologic intervention exists so far. The only available drug, riluzole, extends the lifespan of ALS patients for not more than 2-3 months. There is a basic lack of information about the pathomechanisms involved in the course of disease initiation and progression, especially how proposed cytopathological events interact with each other in a disease typical manner. Beyond motor neuron degeneration, there is strong evidence that the relentless disorder has further systemic implications. ALS patients frequently experience single or multiple misdiagnosis. The average time from disease onset to correct diagnosis is 12 months. This is particularly significant when one considers that most of the ALS patients die within 2-5 years after disease onset. In fact, delayed diagnosis times hamper research on early diagnostic markers, whereas short survival times come along with narrow time windows to study disease-modifying factors or even to define therapeutic end points in the course of intervention studies. The current chapter gives a review about the progress in biomarker research based on genetic, proteomic, and metabolomic (candidate) markers reported so far.