title: Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis.
abstract: Glatiramer acetate (GA) is a disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) with several putative mechanisms of action. Currently, there is paucity of in vivo human data linking the well-established peripheral immunologic effects of therapy with GA to its potential effects inside the central nervous system (CNS). Brain proton magnetic resonance spectroscopy (MRS) allows in vivo examination of axonal integrity by quantifying the resonance intensity of the neuronal marker N-acetylaspartate (NAA). In a pilot study to investigate the effect of GA on axonal injury, we performed combined brain magnetic resonance imaging (MRI) and MRS studies in 18 treatment naïve RRMS patients initiating therapy with GA at baseline and annually for two years on therapy. A small group of four treatment naïve RRMS patients, electing to remain untreated, served as controls. NAA/Cr was measured in a large central brain volume of interest (VOI) as well as the normal appearing white matter (NAWM) within the VOI. After two years, NAA/Cr in the GA-treated group increased significantly by 10.7% in the VOI (2.17 +/- 0.26 versus 1.96 +/- 0.24, P = 0.03) and by 71% in the NAWM (2.23 +/- 0.26 versus 2.08 +/- 0.31, P = 0.04). In the untreated group, NAA/Cr decreased by 8.9% at two years in the VOI (2.01 +/- 0.16 versus 1.83 +/- 0.21, P = 0.03) and 8.2% in the NAWM (2.07 +/- 0.24 versus 1.90 +/- 0.29, P = 0.03). Our data shows that treatment with GA leads to axonal metabolic recovery and protection from sub-lethal axonal injury. These results support an in situ effect of GA therapy inside the CNS and suggest potential neuroprotective effects of GA.
authors.affiliation: Department of Neurology, Multiple Sclerosis Center, Wayne State University School of Medicine, Detroit, MI 48201, USA. okhan@med.wayne.edu
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
authors.forename: Yimin
authors.initials: Y
authors.lastname: Shen
authors.forename: Christina
authors.initials: C
authors.lastname: Caon
authors.forename: Fen
authors.initials: F
authors.lastname: Bao
authors.forename: Wendy
authors.initials: W
authors.lastname: Ching
authors.forename: Melissa
authors.initials: M
authors.lastname: Reznar
authors.forename: Alyssa
authors.initials: A
authors.lastname: Buccheister
authors.forename: Jiani
authors.initials: J
authors.lastname: Hu
authors.forename: Zahid
authors.initials: Z
authors.lastname: Latif
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tselis
authors.forename: Robert
authors.initials: R
authors.lastname: Lisak
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology; D003401:Creatine / Q000378:metabolism; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage*; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D010455:Peptides; D001224:Aspartic Acid; D000068717:Glatiramer Acetate; C000179:N-acetylaspartate; D003401:Creatine