To investigate disease modifying effects of prophylactic glatiramer acetate (GA) treatment in the opticospinal encephalomyelitis (OSE) mouse model.

GA is a well-established treatment option for patients with relapsing-remitting multiple sclerosis with few side effects. Its detailed immunomodulatory mechanism of action is still unknown. OSE represents a double-transgenic mouse model for spontaneous EAE with recombinant T- and B-cells for myelin oligodendrocyte glycoprotein MOG_35-55 antigen. While negligible effects of GA on OSE have been reported in a small study, its effects in a large cohort have not been investigated so far.

OSE mice without clinical symptoms were treated once daily either with 150 µl GA (n=18) or 150 µl vehicle (n=20) intraperitoneally (i.p.). Animals were scored daily regarding clinical signs (scoring from 0=no symptoms, 7=severe paraparesis/paraplegia,10=death) and weight. Animals were sacrificed after 30 days of treatment or after having reached a score of 7.0 due to animal care guidelines. Fluorescence-activated cell sorting of immune cells and immunohistochemistry of spinal cord sections were performed.

Preventive treatment with 150 µl GA i.p. once daily significantly reduced clinical disease progression (mean score ± SEM at day 30: GLAT 3.9 ± 1.0; control 6.2 ± 0.7; p=0.0015) in accordance with positive effects on weight. Immune cell composition of secondary lymphoid organs was unchanged. Immunohistochemistry revealed a significant, modest reduction of Iba1⁺ cells while F4/80⁺ cells modestly increased upon GLAT treatment. General inflammation, demyelination or CD11c⁺ dendritic cell infiltration did not differ.

Preventive treatment with GA reduces disease progression in the OSE mouse model in line with modest effects on microglia/macrophages. Due to the lack of established prophylactic treatment options for chronic autoimmune diseases with high risk of disability, our study could provide valuable indications for translational medicine. Further studies are warranted to elucidate the mechanism of action of GLAT.