Decreased microglial activation in MS patients treated with glatiramer acetate.

Abstract

Activated microglia are thought to be an important contributor to tissue damage in multiple sclerosis (MS). The level of microglial activation can be measured non-invasively using [(11)C]-R-PK11195, a radiopharmaceutical for positron emission tomography (PET). Prior studies have identified abnormalities in the level of [(11)C]-R-PK11195 uptake in patients with MS, but treatment effects have not been evaluated. Nine previously untreated relapsing-remitting MS patients underwent PET and magnetic resonance imaging of the brain at baseline and after 1 year of treatment with glatiramer acetate. Parametric maps of [(11)C]-R-PK11195 uptake were obtained for baseline and post-treatment PET scans, and the change in [(11)C]-R-PK11195 uptake pre- to post-treatment was evaluated across the whole brain. Region-of-interest analysis was also applied to selected subregions. Whole brain [(11)C]-R-PK11195 binding potential per unit volume decreased 3.17% (95% CI: -0.74, -5.53%) between baseline and 1 year (p = 0.018). A significant decrease was noted in cortical gray matter and cerebral white matter, and a trend towards decreased uptake was seen in the putamen and thalamus. The results are consistent with a reduction in inflammation due to treatment with glatiramer acetate, though a larger controlled study would be required to prove that association. Future research will focus on whether the level of baseline microglial activation predicts future tissue damage in MS and whether [(11)C]-R-PK11195 uptake in cortical gray matter correlates with cortical lesion load.

• Authors: John N Ratchford, Christopher J Endres, Dima A Hammoud, Martin G Pomper, Navid Shiee, John McGready, Dzung L Pham, Peter A Calabresi
• Journal: Journal of neurology (J Neurol) Vol. 259 Issue 6 Pg. 1199-205 (Jun 2012) ISSN: 1432-1459 [Electronic] Germany
• PMID: 22160466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Peptides
• Glatiramer Acetate

Topics

• Adult
• Female
• Glatiramer Acetate
• Humans
• Immunosuppressive Agents (therapeutic use)
• Male
• Microglia (drug effects, metabolism)
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (drug therapy, metabolism)
• Peptides (pharmacology, therapeutic use)
• Protein Binding (physiology)
• Treatment Outcome