Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany.
Cells. 2023 Feb 8;12(4):542. doi: 10.3390/cells12040542.
Glatiramer acetate (GA) is a well-established treatment option for patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis (MS) with few side effects. The double transgenic mouse model spontaneous opticospinal encephalomyelitis (OSE), based on recombinant myelin oligodendrocyte glycoprotein reactive T and B cells, mimicks features of chronic inflammation and degeneration in MS and related disorders. Here, we investigated the effects of prophylactic GA treatment on the clinical course, histological alterations and peripheral immune cells in OSE. To investigate the effects of prophylactic glatiramer acetate (GA) treatment in a mouse model of spontaneous opticospinal encephalomyelitis (OSE). OSE mice with a postnatal age of 21 to 28 days without signs of encephalomyelitis were treated once daily either with 150 µg GA or vehicle intraperitoneally (i. p.). The animals were scored daily regarding clinical signs and weight. The animals were sacrificed after 30 days of treatment or after having reached a score of 7.0 due to animal care guidelines. We performed immunohistochemistry of spinal cord sections and flow cytometry analysis of immune cells. Preventive treatment with 150 µg GA i. p. once daily significantly reduced clinical disease progression with a mean score of 3.9 ± 1.0 compared to 6.2 ± 0.7 in control animals ( < 0.01) after 30 d in accordance with positive effects on weight ( < 0.001). The immunohistochemistry showed that general inflammation, demyelination or CD11c dendritic cell infiltration did not differ. There was, however, a modest reduction of the Iba1 area ( < 0.05) and F4/80 area upon GA treatment ( < 0.05). The immune cell composition of secondary lymphoid organs showed a trend towards an upregulation of regulatory T cells, which lacked significance. Preventive treatment with GA reduces disease progression in OSE in line with modest effects on microglia/macrophages. Due to the lack of established prophylactic treatment options for chronic autoimmune diseases with a high risk of disability, our study could provide valuable indications for translational medicine.
醋酸格拉替雷（GA）是一种治疗临床孤立综合征和复发缓解型多发性硬化症（MS）的有效方法，副作用较少。基于重组髓鞘少突胶质细胞糖蛋白反应性 T 和 B 细胞的双转基因小鼠自发视神经脊髓炎（OSE）模型模拟了 MS 和相关疾病的慢性炎症和退行性变的特征。在这里，我们研究了预防性 GA 治疗对 OSE 的临床病程、组织学改变和外周免疫细胞的影响。
在自发性视神经脊髓炎（OSE）小鼠模型中研究预防性醋酸格拉替雷（GA）治疗的效果。
将出生后 21-28 天无脊髓炎迹象的 OSE 小鼠，每日腹腔内（i. p.）给予 150μg GA 或载体治疗。每日对动物进行临床症状和体重评分。根据动物护理指南，治疗 30 天后或因动物护理而达到 7.0 分后处死动物。我们对脊髓切片进行免疫组织化学染色，对免疫细胞进行流式细胞术分析。
预防性每日腹腔内给予 150μg GA 可显著降低临床疾病进展，与对照组相比，30 天后平均评分分别为 3.9±1.0 和 6.2±0.7（<0.01），同时对体重也有积极影响（<0.001）。免疫组织化学显示，一般炎症、脱髓鞘或 CD11c 树突状细胞浸润无差异。然而，GA 治疗后 Iba1 区域（<0.05）和 F4/80 区域（<0.05）略有减少。次级淋巴器官的免疫细胞组成显示调节性 T 细胞有上调趋势，但无统计学意义。
GA 的预防性治疗可降低 OSE 中的疾病进展，同时对小胶质细胞/巨噬细胞有适度影响。由于慢性自身免疫性疾病具有高致残风险，缺乏既定的预防性治疗方法，因此我们的研究可能为转化医学提供有价值的依据。
