Luccarini Ilaria, Ballerini Clara, Biagioli Tiziana, Biamonte Filippo, Bellucci Arianna, Rosi Maria Cristina, Grossi Cristina, Massacesi Luca, Casamenti Fiorella
Department of Pharmacology, University of Florence, Viale Pieraccini n. 6, Florence, Italy.
Exp Neurol. 2008 May;211(1):214-26. doi: 10.1016/j.expneurol.2008.01.022. Epub 2008 Feb 14.
Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). An approach to improve MS treatment is to identify a rational combination of new medications or existing therapies that impact different aspects of the disease process. Statins are effective in the treatment of MS animal models and are promising candidates for future treatment. Minocycline ameliorates clinical severity of experimental autoimmune encephalomyelitis (EAE) and exhibits several anti-inflammatory and neuroprotective activities. In this study, we tested whether the combination of these two drugs could produce beneficial effects in EAE mice immunized with myelin oligodendrocyte protein (MOG). Our findings show that combined treatment, compared to using the medications alone, resulted in a significant reduction in disease severity, in both the acute and chronic phases of the disease, along with attenuation of inflammation, demyelination and axonal loss. Stereological analysis revealed that the combined treatment significantly guarded against neuroinflammation and neurodegeneration. Moreover, a significant suppression of anti-MOG antibody production in animals treated with the two medications was found. In conclusion, our findings prove that this combination of drugs is neuroprotective and suppresses the severity of EAE. Furthermore, this pharmacological approach appears to be promising as a future therapeutic strategy to control MS.
多发性硬化症(MS)是中枢神经系统(CNS)最常见的炎性脱髓鞘疾病。改善MS治疗的一种方法是确定影响疾病进程不同方面的新药物或现有疗法的合理组合。他汀类药物在MS动物模型治疗中有效,是未来治疗的有前景的候选药物。米诺环素可改善实验性自身免疫性脑脊髓炎(EAE)的临床严重程度,并具有多种抗炎和神经保护活性。在本研究中,我们测试了这两种药物的组合是否能在用髓鞘少突胶质细胞糖蛋白(MOG)免疫的EAE小鼠中产生有益效果。我们的研究结果表明,与单独使用药物相比,联合治疗在疾病的急性期和慢性期均导致疾病严重程度显著降低,同时炎症、脱髓鞘和轴突损失减轻。体视学分析显示,联合治疗可显著预防神经炎症和神经退行性变。此外,在用这两种药物治疗的动物中发现抗MOG抗体产生受到显著抑制。总之,我们的研究结果证明,这种药物组合具有神经保护作用,并可抑制EAE的严重程度。此外,这种药理学方法作为未来控制MS的治疗策略似乎很有前景。