title: Hypothesis: a motor neuron toxin produced by a clostridial species residing in gut causes ALS.
abstract: We hypothesize that a yet-to-be-identified motor neuron toxin produced by a clostridial species causes sporadic amyotrophic lateral sclerosis (ALS) in susceptible individuals. This clostridial species would reside undetected in the gut and chronically produce a toxin that targets the motor system, like the tetanus and botulinum toxins. After gaining access to the lower motor neuron, the toxin would be transported back to the cell body, as occurs with the tetanus toxin, and destroy the lower motor neuron - the essential feature of ALS. Again like the tetanus toxin, some of the toxin would cross to neighboring cells and to the upper motor neuron and similarly destroy these motor neurons. Weakness would relentlessly progress until not enough motor neurons remained to sustain life. If this hypothesis were correct, treatment with appropriate antibiotics or antitoxins might slow or halt progression of disease, and immunization might prevent disease.
authors.affiliation: Department of Neurology, School of Medicine, University of Washington, Seattle, Washington, USA. wl@u.washington.edu
authors.forename: W T
authors.initials: WT
authors.lastname: Longstreth
authors.forename: J S
authors.initials: JS
authors.lastname: Meschke
authors.forename: S K
authors.initials: SK
authors.lastname: Davidson
authors.forename: L M
authors.initials: LM
authors.lastname: Smoot
authors.forename: J C
authors.initials: JC
authors.lastname: Smoot
authors.forename: T D
authors.initials: TD
authors.lastname: Koepsell
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000382:microbiology / Q000517:prevention & control; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001370:Axonal Transport; D001427:Bacterial Toxins / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D001681:Biological Assay; D001692:Biological Transport; D003013:Clostridium / Q000472:pathogenicity*; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008954:Models, Biological; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology; D009498:Neurotoxins / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D011498:Protein Precursors / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D005732:Gangliosides; D009498:Neurotoxins; D011498:Protein Precursors