title: [Research in amyotrophic lateral sclerosis: what is new in 2009?].
abstract: This paper, written by French amyotrophic lateral sclerosis (ALS) center experts, presents an update of recent advances in fundamental, epidemiological and clinical research in ALS based on a review of the literature between September 2008 and November 2009. Among other pathophysiological mechanisms, the role of stress of the endoplasmic reticulum and the importance of energetic metabolic disturbances have been underscored. In the field of genetics, research has been advanced through the identification of mutations of the gene FUsed in Sarcoma/Translated in LipoSarcoma (FUS/TLS) in individuals with familial and sporadic ALS. This gene is involved in the regulation of transcription, splicing and RNA transport, and has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration. A report showed that mice expressing a mutant form of human TDP-43 develop a progressive and fatal neurodegenerative disease reminiscent of both ALS and frontotemporal lobar degeneration with ubiquitin aggregates (FTLD-U), providing a new animal model that may help to better understand the pathophysiology and test new therapeutics. Beside genetic studies, several epidemiologic studies have investigated the role of environmental factors. A recent study suggests that smoking is a risk factor for developing ALS and it is hypothesized that this could occur through lipid peroxidation via formaldehyde exposure. From a neuroprotective perspective, trials with IGF-1, sodium valproate, coenzyme Q or glatiramer acetate have failed to demonstrate any beneficial effect. A study published in 2008 argued that lithium may have a neuroprotective effect in ALS mice and also in patients. However, two preclinical studies failed to replicate the neuroprotective effect of lithium in ALS mice. Therapeutic trials have been performed or are currently ongoing in Europe and North America. Their results have not yet been published.
authors.affiliation: CHU Pitié-Salpêtrière, AP-HP, Paris cedex 13, France. pierre-francois.pradat@psl.ap-hop-paris.fr
authors.forename: P-F
authors.initials: PF
authors.lastname: Pradat
authors.forename: S
authors.initials: S
authors.lastname: Attarian
authors.forename: J-P
authors.initials: JP
authors.lastname: Camdessanché
authors.forename: L
authors.initials: L
authors.lastname: Carluer
authors.forename: P
authors.initials: P
authors.lastname: Cintas
authors.forename: P
authors.initials: P
authors.lastname: Corcia
authors.forename: A
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez-Bermejo
authors.forename: N
authors.initials: N
authors.lastname: Guy
authors.forename: G
authors.initials: G
authors.lastname: Nicolas
authors.forename: T
authors.initials: T
authors.lastname: Perez
authors.forename: M-H
authors.initials: MH
authors.lastname: Soriani
authors.forename: N
authors.initials: N
authors.lastname: Vandenberghe
authors.forename: A
authors.initials: A
authors.lastname: Verschueren
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D015415:Biomarkers; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004781:Environmental Exposure; D006801:Humans; D044342:Malnutrition / Q000209:etiology / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D034702:RNA-Binding Protein FUS / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000072105:Superoxide Dismutase-1
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D018696:Neuroprotective Agents; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1