title: Muscle gene expression is a marker of amyotrophic lateral sclerosis severity.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset degenerative disease characterized by the loss of upper and lower motor neurons leading to progressive muscle atrophy and paralysis. The lack of molecular markers of the progression of disease is detrimental to clinical practice and therapeutic trials.
  
  
  OBJECTIVE
  This study was designed to identify gene expression changes in skeletal muscle that could reliably define the degree of disease severity.
  
  
  METHODS
  Gene expression profiles were obtained from the deltoid muscles of ALS patients and healthy subjects. Changes in differentially expressed genes were compared to the status of deltoid muscle disability, as determined by manual muscle testing, electrophysiology and the degree of myofiber atrophy. Functionally related genes were grouped by annotation analysis, and deltoid muscle injury was predicted using binary tree classifiers.
  
  
  RESULTS
  Two sets of 25 and 70 transcripts appeared differentially regulated exclusively in early and advanced states of deltoid muscle impairment, respectively. The expression of another set of 198 transcripts correlated with a composite score of muscle injury combining manual muscle testing and histological examination. From the totality of these expression changes, 155 transcripts distinguished advanced from early deltoid muscle impairment with 80% sensitivity and 100% specificity. Nine of these transcripts, known also to be regulated in ALS mouse and surgically denervated muscle, predicted the advanced disease status with 100% sensitivity and specificity.
  
  
  CONCLUSIONS
  We provide robust gene expression changes that can be of practical use when monitoring ALS status and the effects of disease-modifying drugs.
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Fédération des Maladies du Système Nerveux, Centre Référent Maladie Rare SLA, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.forename: Odile
authors.initials: O
authors.lastname: Dubourg
authors.forename: Marc
authors.initials: M
authors.lastname: de Tapia
authors.forename: Franck
authors.initials: F
authors.lastname: di Scala
authors.forename: Luc
authors.initials: L
authors.lastname: Dupuis
authors.forename: Timothee
authors.initials: T
authors.lastname: Lenglet
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bruneteau
authors.forename: François
authors.initials: F
authors.lastname: Salachas
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Corvol
authors.forename: Philippe
authors.initials: P
authors.lastname: Demougin
authors.forename: Michael
authors.initials: M
authors.lastname: Primig
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Gonzalez de Aguilar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D057645:Deltoid Muscle / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009133:Muscular Atrophy
chemical_list: D005819:Genetic Markers