title: 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.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe St, Pathology 627, Baltimore, MD 21287-6985, USA. jratchf1@jhmi.edu
authors.forename: John N
authors.initials: JN
authors.lastname: Ratchford
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Endres
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Navid
authors.initials: N
authors.lastname: Shiee
authors.forename: John
authors.initials: J
authors.lastname: McGready
authors.forename: Dzung L
authors.initials: DL
authors.lastname: Pham
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate