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Decreased microglial activation in MS patients treated with glatiramer acetate

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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 [11C]-R-PK11195, a radiopharmaceutical for positron emission tomography (PET). Prior studies have identified abnormalities in the level of [11C]-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 [11C]-R-PK11195 uptake were obtained for baseline and post-treatment PET scans, and the change in [11C]-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 [11C]-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 [11C]-R-PK11195 uptake in cortical gray matter correlates with cortical lesion load.

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Acknowledgments

This study was funded by an independent medical grant from TEVA Neuroscience to Dr. Calabresi. The study sponsor had no role in the design or execution of the study, data analysis, manuscript preparation, or decision to submit the paper for publication.

Conflict of interest

Dr. Ratchford receives research support from the Nancy Davis Foundation for Multiple Sclerosis and support for clinical trials from Novartis and Biogen Idec. Dr. Endres, Dr. Hammoud, Dr. Pomper, Mr. Shiee, Dr. McGready, Dr. Pham have nothing to disclose. Dr. Calabresi has received personal compensation for consulting, serving on scientific advisory boards and speaking activities from Biogen-IDEC, Teva, Merck-Serono, Novartis, Vertex, Vaccinex, Genzyme, and Abbott. He has received research funding from Biogen-IDEC, Teva, EMD-Serono, Vertex, Genentech, Abbott, and Bayer.

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Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe St., Pathology 627, Baltimore, MD, 21287-6985, USA

    John N. Ratchford & Peter A. Calabresi

  2. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Christopher J. Endres, Dima A. Hammoud, Martin G. Pomper & Navid Shiee

  3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    John McGready

  4. Department of Electrical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Dzung L. Pham

  5. Center for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, MD, USA

    Dzung L. Pham

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  1. John N. Ratchford
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  2. Christopher J. Endres
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  8. Peter A. Calabresi
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Correspondence to John N. Ratchford.

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Ratchford, J.N., Endres, C.J., Hammoud, D.A. et al. Decreased microglial activation in MS patients treated with glatiramer acetate. J Neurol 259, 1199–1205 (2012). https://doi.org/10.1007/s00415-011-6337-x

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  • DOI: https://doi.org/10.1007/s00415-011-6337-x

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