Decreased microglial activation in MS patients treated with glatiramer acetate

John N. Ratchford, Christopher J. Endres, Dima A. Hammoud, Martin Gilbert Pomper, Navid Shiee, John McGready, Dzung L. Pham, Peter Calabresi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1199-1205
Number of pages7
JournalJournal of Neurology
Volume259
Issue number6
DOIs
StatePublished - Jun 2012

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Multiple Sclerosis
Positron-Emission Tomography
Brain
Therapeutics
Relapsing-Remitting Multiple Sclerosis
Radiopharmaceuticals
Putamen
Microglia
Thalamus
Glatiramer Acetate
(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide
Magnetic Resonance Imaging
Inflammation
Gray Matter

Keywords

  • Copolymer 1
  • Immunology
  • Microglia
  • Multiple sclerosis
  • PK11195
  • Positron emission tomography

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Decreased microglial activation in MS patients treated with glatiramer acetate. / Ratchford, John N.; Endres, Christopher J.; Hammoud, Dima A.; Pomper, Martin Gilbert; Shiee, Navid; McGready, John; Pham, Dzung L.; Calabresi, Peter.

In: Journal of Neurology, Vol. 259, No. 6, 06.2012, p. 1199-1205.

Research output: Contribution to journalArticle

Ratchford, John N. ; Endres, Christopher J. ; Hammoud, Dima A. ; Pomper, Martin Gilbert ; Shiee, Navid ; McGready, John ; Pham, Dzung L. ; Calabresi, Peter. / Decreased microglial activation in MS patients treated with glatiramer acetate. In: Journal of Neurology. 2012 ; Vol. 259, No. 6. pp. 1199-1205.
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