Glatiramer acetate guards against rapid memory decline during relapsing-remitting experimental autoimmune encephalomyelitis.

Cognitive decline presents a therapeutic challenge for patients with multiple sclerosis (MS), a disease characterized by recurrent autoimmune demyelination and by progressive CNS degeneration. Glatiramer acetate (GA, also known as Copolymer 1, Cop-1, or Copaxone), commonly used to treat MS, reduces the frequency of relapses; it has both anti-inflammatory and neuroprotective properties. However, clinical trials have not definitively shown that GA improves cognitive impairment during MS. Using an in vivo animal model of autoimmune demyelination, i.e., relapsing-remitting experimental autoimmune encephalomyelitis (EAE), we tested short-term memory in EAE mice (EAE), in EAE mice treated with GA for 10 days starting at the time of immunization (EAE + GA), and in age-matched healthy, naïve mice (Naïve). Short-term memory was assessed using the cross-maze test at 10, 20, and 30 days post-immunization (d.p.i.); data were analyzed at each time point and over time. At 10 d.p.i., EAE and EAE + GA mice had better memory function than Naïve mice. However, at the later time points, EAE mice had a steep negative slope of memory function (indicating decline), whereas EAE + GA mice had a flatter, less-negative slope of memory function. Notably, the memory function of EAE mice significantly decreased over time compared with that of Naïve mice, indicating that EAE had a negative impact on cognitive ability. In contrast, there was no statistically significant difference between the slopes of memory function in mice with EAE treated with GA versus Naïve mice, which revealed effective, albeit partial, protection by GA treatment against progressive memory decline during EAE disease. Of particular interest, although EAE mice had memory decline over 30 d.p.i., their clinical disease scores improved during that time. Thus, our results suggest that EAE mice had a significant progressive memory decline and that GA, administered at the time of immunization, partially guards against rapid memory decline.