Combined treatment with atorvastatin and minocycline suppresses severity of EAE.
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.
Luccarini
Ilaria
I
Department of Pharmacology, University of Florence, Viale Pieraccini n. 6, Florence, Italy.
Ballerini
Clara
C
Biagioli
Tiziana
T
Biamonte
Filippo
F
Bellucci
Arianna
A
Rosi
Maria Cristina
MC
Grossi
Cristina
C
Massacesi
Luca
L
Casamenti
Fiorella
F
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009460:Neurologic Examination; D010446:Peptide Fragments / Q000494:pharmacology; D011758:Pyrroles / Q000627:therapeutic use*; D013238:Stereotaxic Techniques; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors
D000900:Anti-Bacterial Agents; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011758:Pyrroles; C445081:myelin oligodendrocyte glycoprotein (35-55); D000069059:Atorvastatin; D008911:Minocycline