Increase in serum levels of uric acid,an endogenous antioxidant,under treatment with glatiramer acetate for multiple sclerosis

Abstract

Free radicals including peroxynitrite are induced in Multiple Sclerosis (MS). Antioxidant and peroxynitrite inhibitor uric acid (UA), suppresses the MS animal model experimental autoimmune encephalomyelitis (EAE). MS patients have lower average serum UA than controls. An inverse relationship exists between MS and gout. Glatiramer acetate (GA) suppresses EAE and is beneficial in relapsing MS. We investigated serum UA changes during open-label treatment of relapsing MS with GAA. Ten patients (six females, four males, aged 19 to 39 years, mean age 32 years) completed 6 months of GAA (Copaxone® 20 mg s.c. daily). Of these, nine completed 12 months. After 6 months on GAA, serum UA (normal, 173-359 mmol/ml for women, 258-491 mmol/ml for men) increased in nine and marginally decreased (302 to 300 mmol/ml) in a single patient. Mean UA significantly increased from 240 to 303 mol/ml (P=0.0014). At 12 months, UA remained significantly higher than at start (P=0.006) decreasing in only one patient. In contrast, we found no significant UA changes after 6 and 12 months of treatment in 21 MS patients treated with interferon b1-a (Avonex®), or in 11 treated with interferon b1-a (Rebif®), or in five placebo-treated controls. Increasing UA, a natural inhibitor of free radicals, may represent a mechanism of action of glatiramer acetate in MS.

Keywords

glatiramer acetate multiple sclerosis uric acid peroxynitrite reactive nitrogen intermediates reactive oxygen intermediates

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