Neuroprotection with glatiramer acetate: evidence from the PreCISe trial

J Neurol. 2013 Jul;260(7):1901-6. doi: 10.1007/s00415-013-6903-5. Epub 2013 Apr 16.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Axons / drug effects
  • Axons / pathology
  • Brain / drug effects*
  • Brain / pathology
  • Demyelinating Diseases / drug therapy*
  • Demyelinating Diseases / pathology
  • Double-Blind Method
  • Female
  • Glatiramer Acetate
  • Humans
  • Male
  • Middle Aged
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Peptides / pharmacology
  • Peptides / therapeutic use*


  • Neuroprotective Agents
  • Peptides
  • Glatiramer Acetate