Amyotrophic Lateral Sclerosis: An Update for 2018

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons and other neuronal cells, leading to severe disability and eventually death from ventilatory failure. It has a prevalence of 5 in 100,000, with an incidence of 1.7 per 100,000, reflecting short average survival. The pathogenesis is incompletely understood, but defects of RNA processing and protein clearance may be fundamental. Repeat expansions in the chromosome 9 open reading frame 72 gene (C9orf72) are the most common known genetic cause of ALS and are seen in approximately 40% of patients with a family history and approximately 10% of those without. No environmental risk factors are proved to be causative, but many have been proposed, including military service. The diagnosis of ALS rests on a history of painless progressive weakness coupled with examination findings of upper and lower motor dysfunction. No diagnostic test is yet available, but electromyography and genetic tests can support the diagnosis. Care for patients is best provided by a multidisciplinary team, and most interventions are directed at managing symptoms. Two medications with modest benefits have Food and Drug Administration approval for the treatment of ALS: riluzole, a glutamate receptor antagonist, and, new in 2017, edaravone, a free radical scavenger. Many other encouraging treatment strategies are being explored in clinical trials for ALS; herein we review stem cell and antisense oligonucleotide gene therapies.

Antioxidants and Nanotechnology: Promises and Limits of Potentially Disruptive Approaches in the Treatment of Central Nervous System Diseases

“…Currently, there are no therapies for ALS, and only two drugs have been clinically approved. The first one is riluzole, a drug targeting excitotoxicity, the second one is edavarone, an antioxidant agent able to scavenge lipid peroxides and hydroxyl radicals . However, both these therapies only provide a mitigation of the symptoms .…”

Nonnative structure in a peptide model of the unfolded state of superoxide dismutase 1 (SOD1): Implications for ALS-linked aggregation

“…Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder affecting motor neuron cells, where it causes progressive loss of muscle control and eventual death (1,2). Patients afflicted with ALS often only survive 2-3 years after the initial onset of symptoms, demonstrating the rapid and invariably fatal effects of the disease.…”

Zinc Transporter-3 Knockout Mice Demonstrate Age-Dependent Alterations in the Metalloproteome

“…It is a similar scenario for the antioxidant enzyme copper-zinc superoxide dismutase (Cu, Zn-SOD), which exists as two isoforms (SOD1 and SOD3, having activity primarily in the cytoplasm and extracellular space respectively). SOD1 is implicated in the pathogenesis of amyotrophic lateral sclerosis [24], a rare disease that primarily results in the degeneration of upper and lower motor neurons leading to muscle paralysis and atrophy, but which is also associated with other non-motor symptoms [25,26]. SOD1 mutations account for~15%-30% of familial ALS cases, depending upon the specific population.…”