TY - JOUR
T1 - Amyotrophic Lateral Sclerosis
T2 - An Update for 2018
AU - Oskarsson, Björn
AU - Gendron, Tania F.
AU - Staff, Nathan P.
N1 - Publisher Copyright:
© 2018 Mayo Foundation for Medical Education and Research
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85049338734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049338734&partnerID=8YFLogxK
U2 - 10.1016/j.mayocp.2018.04.007
DO - 10.1016/j.mayocp.2018.04.007
M3 - Review article
C2 - 30401437
AN - SCOPUS:85049338734
SN - 0025-6196
VL - 93
SP - 1617
EP - 1628
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 11
ER -