title: Neuroprotection with glatiramer acetate: evidence from the PreCISe trial.
abstract: The phase III, multicenter, randomized, placebo-controlled PreCISe trial assessed glatiramer acetate (GA) effects in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). To assess the neuroprotective effect of GA in a subset of patients in the PreCISe trial, we used proton magnetic resonance spectroscopy (MRS) to measure N-acetylaspartate (NAA), a marker of neuronal integrity, in a large central volume of brain. Thirty-four CIS patients randomized to GA 20 mg/day (n = 19) SC or placebo (n = 15) were included. Patients who relapsed (developed clinically definite MS [CDMS]) were removed from the substudy. NAA/creatine (NAA/Cr) ratios were compared between GA-treated and placebo-treated patients. Twenty patients with CIS had not converted to CDMS and were still in the double-blind phase of the trial at 12 months of follow-up. Paired changes in NAA/Cr differed significantly in patients treated with GA (+0.14, n = 11) compared with patients receiving placebo (-0.33, n = 9, p = 0.03) at 12 months, consistent with a neuroprotective effect of GA in vivo. Patients with CIS who received GA showed improvement in brain neuroaxonal integrity, as indicated by increased NAA/Cr, relative to comparable patients treated with placebo, who showed a decline in NAA/Cr consistent with findings from natural history studies.
authors.affiliation: NeuroRx Research, 3605 University Street, Montreal, QC, H3A 2B3, Canada. darnold@neurorx.com
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
authors.forename: Sridar
authors.initials: S
authors.lastname: Narayanan
authors.forename: Samson
authors.initials: S
authors.lastname: Antel
mesh_terms: D000328:Adult; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D000068717:Glatiramer Acetate