TY - JOUR
T1 - Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS
T2 - Pathway to discovery of etiology via lifetime exposome research
AU - Spencer, Peter S.
AU - Palmer, Valerie S.
AU - Kisby, Glen E.
AU - Lagrange, Emmeline
AU - Horowitz, B. Zane
AU - Valdes Angues, Raquel
AU - Reis, Jacques
AU - Vernoux, Jean Paul
AU - Raoul, Cédric
AU - Camu, William
N1 - Publisher Copyright:
Copyright © 2023 Spencer, Palmer, Kisby, Lagrange, Horowitz, Valdes Angues, Reis, Vernoux, Raoul and Camu.
PY - 2023
Y1 - 2023
N2 - The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.
AB - The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.
KW - agaritine
KW - genotoxin
KW - gyromitrin
KW - lifetime exposome
KW - methylazoxymethanol (MAM)
KW - monomethylhydrazine (MMH)
KW - motor neuron disease
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U2 - 10.3389/fnins.2023.1005096
DO - 10.3389/fnins.2023.1005096
M3 - Review article
AN - SCOPUS:85149403766
SN - 1662-4548
VL - 17
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 1005096
ER -