Fluid biomarkers for amyotrophic lateral sclerosis: a review

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. Presently, three FDA-approved drugs are available to help slow functional decline for patients with ALS, but no cure yet exists. With an average life expectancy of only two to five years after diagnosis, there is a clear need for biomarkers to improve the care of patients with ALS and to expedite ALS treatment development. Here, we provide a review of the efforts made towards identifying diagnostic, prognostic, susceptibility/risk, and response fluid biomarkers with the intent to facilitate a more rapid and accurate ALS diagnosis, to better predict prognosis, to improve clinical trial design, and to inform interpretation of clinical trial results. Over the course of 20 + years, several promising fluid biomarker candidates for ALS have emerged. These will be discussed, as will the exciting new strategies being explored for ALS biomarker discovery and development.

MS785-MS27 Reactive Misfolded/Non-Native Zn-Deficient SOD1 Species Exhibit Cytotoxicity and Adopt Heterozygous Conformations in Motor Neurons

“…One of the major issues in clinical research on ALS is that its diagnosis is often delayed due to the need to rule out other neurological diseases with similar symptoms [ 53 ]. Thus, the establishment of a simple test that can definitively diagnose ALS is eagerly anticipated.…”

“…Thus, the establishment of a simple test that can definitively diagnose ALS is eagerly anticipated. In particular, biomarkers to predict disease development or progression would be required for presymptomatic sporadic ALS cases with no genetic predisposition [ 53 ]. We recently reported that cerebrospinal fluid from sporadic ALS cases contains various conformation-disordered WT SOD1 species [ 54 ], which opens up new avenues for the use of conformation-disordered WT SOD1 species as biomarkers for the diagnosis of sporadic ALS.…”

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

“…ALS is a devastating upper motor neuron disease [ 163 ] with unknown pathogenesis [ 164 , 165 ] and no effective treatment. As a result, despite efforts to identify unique biomarkers [ 166 , 167 ], there is still no objective way to prognosticate ALS. Typically, the onset of this disease is in late midlife, and is mostly fatal within 3–5 years after the detection of the first symptoms [ 168 , 169 ].…”