{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dalla Bella E"],"funding":["Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica","Ricerca Corrente of the Ministry of Health to the Fondazione IRCCS Istituto Neurologico “Carlo Besta” of Milan"],"pagination":["2635-2647"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8557337"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["144(9)"],"pubmed_abstract":["Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eIF2α-phosphatase, allowing misfolded protein clearance, reduces neuronal death and prolongs survival in in vitro and in vivo models. However, its safety and efficacy in patients with ALS are unknown. To address these issues, we conducted a multicentre, randomized, double-blind trial with a futility design. Patients with ALS who had displayed an onset of symptoms within the previous 18 months were randomly assigned in a 1:1:1:1 ratio to receive 64 mg, 32 mg or 16 mg of guanabenz or placebo daily f"],"journal":["Brain : a journal of neurology"],"pubmed_title":["The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial."],"pmcid":["PMC8557337"],"funding_grant_id":["2014–005367-32","FGCR 01/2013"],"pubmed_authors":["Corbo M","Lauria G","Dalla Bella E","Simone I","Abgueguen E","Spataro R","Volanti P","Nolan JM","Filosto M","Giannini F","Silani V","Tugnoli V","Riva N","Caponnetto C","Siciliano G","Messina S","Capasso M","Mandrioli J","Verriello L","Bersano E","Tramacere I","Mora G","Monsurro MR","Chio A","Rizzi R","Furlan R","Antonini G","Borghero G","Lunetta C","Soraru G"],"additional_accession":[]},"is_claimable":false,"name":"The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial.","description":"Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eIF2α-phosphatase, allowing misfolded protein clearance, reduces neuronal death and prolongs survival in in vitro and in vivo models. However, its safety and efficacy in patients with ALS are unknown. To address these issues, we conducted a multicentre, randomized, double-blind trial with a futility design. Patients with ALS who had displayed an onset of symptoms within the previous 18 months were randomly assigned in a 1:1:1:1 ratio to receive 64 mg, 32 mg or 16 mg of guanabenz or placebo daily f","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-05-08T05:43:18.635Z","creation":"2022-02-11T12:25:13.961Z"},"accession":"S-EPMC8557337","cross_references":{"pubmed":["33905493"],"doi":["10.1093/brain/awab167"]}}