{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Eshaghi A"],"funding":["Multiple Sclerosis International Federation","Medical Research Council","National Institute for Health Research (NIHR)","Wellcome Trust"],"pagination":["11020-11027"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6561162"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["116(22)"],"pubmed_abstract":["Understanding the mode of action of drugs is a challenge with conventional methods in clinical trials. Here, we aimed to explore whether simvastatin effects on brain atrophy and disability in secondary progressive multiple sclerosis (SPMS) are mediated by reducing cholesterol or are independent of cholesterol. We applied structural equation models to the MS-STAT trial in which 140 patients with SPMS were randomized to receive placebo or simvastatin. At baseline, after 1 and 2 years, patients underwent brain magnetic resonance imaging; their cognitive and physical disability were assessed on the block design test and Expanded Disability Status Scale (EDSS), and serum total cholesterol levels were measured. We calculated the percentage brain volume change (brain atrophy). We compared two mod"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Applying causal models to explore the mechanism of action of simvastatin in progressive multiple sclerosis."],"pmcid":["PMC6561162"],"funding_grant_id":["MC_UP_1401/1","107392/A/15/Z","RG91365","RP-2017-08-ST2-004","MC_UU_00005/9","107392/Z/15/Z","McDonald Fellowship"],"pubmed_authors":["Eshaghi A","Nicholas J","Kievit RA","Sudre CH","Thompson AJ","Barkhof F","Chan D","Cardoso MJ","Prados F","Alexander DC","Ciccarelli O","Nicholas R","Ourselin S","Chataway J","Greenwood J"],"additional_accession":[]},"is_claimable":false,"name":"Applying causal models to explore the mechanism of action of simvastatin in progressive multiple sclerosis.","description":"Understanding the mode of action of drugs is a challenge with conventional methods in clinical trials. Here, we aimed to explore whether simvastatin effects on brain atrophy and disability in secondary progressive multiple sclerosis (SPMS) are mediated by reducing cholesterol or are independent of cholesterol. We applied structural equation models to the MS-STAT trial in which 140 patients with SPMS were randomized to receive placebo or simvastatin. At baseline, after 1 and 2 years, patients underwent brain magnetic resonance imaging; their cognitive and physical disability were assessed on the block design test and Expanded Disability Status Scale (EDSS), and serum total cholesterol levels were measured. We calculated the percentage brain volume change (brain atrophy). We compared two mod","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 May","modification":"2026-05-07T13:24:26.192Z","creation":"2019-07-24T07:15:25Z"},"accession":"S-EPMC6561162","cross_references":{"pubmed":["31072935"],"doi":["10.1073/pnas.1818978116"]}}