title: Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.
abstract: Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.
authors: Department of Biological and Environmental Sciences and Technologies, University of Salento, via Prov.le Lecce-Monteroni, Lecce, Italy.
authors: Lidia
authors: L
authors: De Riccardis
authors: Department of Biological and Environmental Sciences and Technologies, University of Salento, via Prov.le Lecce-Monteroni, Lecce, Italy.
authors: Alessandra
authors: A
authors: Ferramosca
authors: Department of Biological and Environmental Sciences and Technologies, University of Salento, via Prov.le Lecce-Monteroni, Lecce, Italy.
authors: Antonio
authors: A
authors: Danieli
authors: Department of Neurology, "Vito Fazzi" Hospital, ASL-Lecce, Italy.
authors: Giorgio
authors: G
authors: Trianni
authors: Department of Biological and Environmental Sciences and Technologies, University of Salento, via Prov.le Lecce-Monteroni, Lecce, Italy.
authors: Vincenzo
authors: V
authors: Zara
authors: Department of Neurology, "Vito Fazzi" Hospital, ASL-Lecce, Italy.
authors: Francesca
authors: F
authors: De Robertis
authors: Department of Biological and Environmental Sciences and Technologies, University of Salento, via Prov.le Lecce-Monteroni, Lecce, Italy.
authors: Michele
authors: M
authors: Maffia
keywords: CAT, catalase; CD4+ T cells; CNS, central nervous system; CS, citrate synthase; EAE, experimental autoimmune encephalomyelitis; GPX, glutathione peroxidase; GR, glutathione reductase; Glycolysis; HK, hexokinase; MCT, mono-carboxylate transporters; MS, Multiple Sclerosis; Multiple sclerosis; OXPHOS; OXPHOS, oxidative phosphorylation; Oxidative stress; PBMC, peripheral blood mononuclear cell; PFK, phosphofructokinase; RCR, respiratory control ratio; ROS, reactive oxygen species; RRMS, Relapsing-Remitting Multiple Sclerosis; SOD, superoxide dismutase; Th, T helper