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Updated: Apr 6, 2026
Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis
Published on: February 28, 2021
Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing-remitting multiple sclerosis: A
E Fisher1, K Nakamura2, J-C Lee3
1Biogen Inc., Cambridge, USA Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, USA elizabeth.fisher@biogen.com.
Background:
Changes in gray matter (GM) volume may be a useful measure of tissue loss in multiple sclerosis (MS).
Objectives:
To investigate the rate, patterns, and disability correlates of GM volume change in an MS treatment clinical trial.
Methods:
Patients (n=140) with relapsing-remitting MS were randomized to intramuscular (IM) interferon (IFN) beta-1a or placebo. Treatment effects on GM fraction (GMF) and white matter (WM) fraction (WMF) changes, differences in rates of GMF and WMF change in year one and two on treatment, and differences in atrophy rates by disease progression status were assessed retrospectively.
Results:
Significantly less GM atrophy (during year two), but not WM atrophy (at any point), was observed with IM IFN beta-1a compared with placebo. Pseudoatrophy effects were more apparent in WM than in GM; in year one, greater WM volume loss was observed with IM IFN beta-1a than with placebo, whereas GM volume loss was similar between groups. Risk of sustained disability progression was significantly associated with GM, but not WM, atrophy.
Conclusions:
These results suggest that GMF change is more meaningful than WMF as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials.
Insights
Gray matter (GM) volume loss in multiple sclerosis (MS) is linked to disability. Intramuscular interferon beta-1a reduced GM atrophy in year two, suggesting GM changes are key markers for MS trials.
Area of Science:
- Neuroscience
- Clinical Trials
- Biomarkers
Background:
- Gray matter (GM) volume changes are potential indicators of tissue loss in multiple sclerosis (MS).
- Assessing GM and white matter (WM) volume changes is crucial for understanding MS progression and treatment efficacy.
Purpose of the Study:
- To evaluate the rate, patterns, and disability correlations of GM volume changes within a clinical trial for MS treatment.
- To compare the effects of intramuscular (IM) interferon beta-1a versus placebo on GM and WM volume changes over two years.
Main Methods:
- 140 patients with relapsing-remitting MS were randomized to receive either IM interferon beta-1a or placebo.
- Retrospective analysis of GM fraction (GMF) and WM fraction (WMF) changes, including differences in atrophy rates based on disease progression status.
Main Results:
- Intramuscular interferon beta-1a significantly reduced GM atrophy in the second year compared to placebo; WM atrophy was not significantly different.
- Greater WM volume loss occurred with IM interferon beta-1a in year one (pseudoatrophy), while GM loss was similar between groups.
- GM atrophy, not WM atrophy, was significantly associated with the risk of sustained disability progression.
Conclusions:
- Gray matter fraction (GMF) change is a more significant indicator of tissue loss than white matter fraction (WMF) change in MS.
- GMF changes may serve as a valuable biomarker to supplement whole-brain atrophy measurements in multiple sclerosis clinical trials.
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