Thursday, 18 April 2013

Neuroprotection with Glaterimer acetate

Arnold DL, Narayanan S, Antel S Neuroprotection with glatiramer acetate: evidence from the PreCISe trial. J Neurol. 2013 Apr. [Epub ahead of print]

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.
This study looked at the effect of glaterimer acetate on whether there was damage or not whe treatment was initiated at symptom onset. In the PreCISe trial . Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo as reported earlier. The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. In this study they report that when you do magnectic resonance spectroscopy to see brain content of chemicals they see less loss of n acytl asparatate, which is concentrated in nerves. This suggests there is less nerve loss. As we have been saying if you can stop the immune response then you can limit the damage that this will be doing. 

This study however appears biased because they removed the people that got MS from the study so the potential treatment failures we removed.

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