Related Experiment Videos
Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and
1Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
Abstract:
The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsing-remitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image sets from 113 out of 119 patients randomized to GA, and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume was significantly correlated with patients' disability at each time-point. No significant differences between placebo- and GA-treated patients were found for baseline brain volume and rate of brain volume change over the study, even though a possible late trend for treatment with GA to retard the loss of brain volume was observed. There was a significant, but modest, correlation between MRI activity during the double-blind phase, and brain volume change over the entire study among patients originally treated with placebo. The modest correlation between enhancement frequency and brain atrophy loss indicates that the suppression of inflammatory activity in RR multiple sclerosis patients is not fully and rapidly associated with a similar effect on the global neurodegenerative processes. This study also suggests that any effect of GA in preventing brain volume decrease is not evident early following institution of treatment.
Insights
Glatiramer acetate (GA) did not significantly reduce brain atrophy in relapsing-remitting multiple sclerosis (RRMS) patients over 18 months. While some trends suggested a late benefit, early treatment effects on brain volume loss were not evident.
Area of Science:
- Neuroscience
- Radiology
- Pharmacology
Background:
- Multiple Sclerosis (MS) is a chronic neurological disease characterized by inflammation and neurodegeneration.
- Brain atrophy, measured by serial MRI, is a key indicator of MS pathology and disease progression.
- Glatiramer acetate (GA) is an established therapy for relapsing-remitting MS (RRMS), known to impact disease activity.
Purpose of the Study:
- To investigate the effect of Glatiramer acetate (GA) on brain atrophy development in patients with RRMS.
- To assess whether GA treatment influences the rate of brain volume loss over an 18-month period.
Main Methods:
- An 18-month study with a 9-month double-blind, placebo-controlled phase followed by a 9-month open-label phase.
- Patients received either 20 mg GA or placebo subcutaneously daily, with regular brain MRI scans.
- Brain volume was measured using semi-automated segmentation on MRI scans obtained at baseline, end of double-blind, and end of study phases.
Main Results:
- No significant differences in baseline brain volume or the rate of brain volume change were observed between GA and placebo groups.
- A potential late trend for GA to slow brain volume loss was noted, but not statistically significant.
- A modest correlation existed between MRI inflammatory activity and brain volume change in the placebo group, suggesting inflammation suppression doesn't fully halt neurodegeneration.
Conclusions:
- Glatiramer acetate treatment did not demonstrate a significant effect on reducing brain atrophy in RRMS patients within the 18-month study period.
- The study suggests that any potential benefit of GA in preventing brain volume decrease may not be apparent early in treatment.
- Inflammatory activity suppression by GA may not be immediately or fully linked to a reduction in global neurodegenerative processes in RRMS.