Premium
Concurrent Treatment with Lovastatin and 5‐Aminoimidazole‐4‐Carboxamide‐1‐Beta‐D‐Ribofuranoside provides Neuroprotection and alleviate Neurodegeneration in Experimental Autoimmune Encephalomyelitis
Author(s) -
Paintlia Ajaib Singh,
Paintlia Manjeet K,
Singh Avtar K,
Singh Inderjit
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1136
Subject(s) - experimental autoimmune encephalomyelitis , multiple sclerosis , lovastatin , medicine , combination therapy , neuroprotection , immunology , inflammation , myelin , myelin oligodendrocyte glycoprotein , neurodegeneration , pharmacology , disease , central nervous system , cholesterol
Combination therapy, rather than monotherapy, with existing or novel therapeutics is increasingly being recognized as a logical next step in disease treatment due to the complex pathology of Multiple Sclerosis. Earlier, we had documented that both lovastatin and AICAR prevent the progression of Experimental Autoimmune Encephalomyelitis (EAE)by different mechanisms of action. Here, we evaluated the therapeutic efficacy of lovastatin and AICAR combination, to limit the progression of EAE. Suboptimal doses of these drugs in combination had synergistic efficacy against the progression of EAE disease as exemplified by delayed onset of clinical symptoms, degree of severity and duration of disease, compared to individual administration of these drugs. Similarly, there was an additive decrease in cellular infiltration and expression of pro‐inflammatory cytokines with a parallel increase in expression of anti‐inflammatory cytokines in EAE animals with this combination treatment. In addition, the combination treatment biased the class of myelin basic protein‐specific antibodies elicited from IgG2a to IgG1 and IgG2b, suggesting a shift from a Th1 to Th2 phenotype response. Furthermore, combination treatment provided neuro‐protection by lessening the axonal loss and demyelination, and improved neuro‐regeneration and myelin repair in the CNS of EAE animals compared with those treated with lovastatin or AICAR individually. Altogether, these data revealed that combination therapy with lovastatin and AICAR is a better approach to avert the progression of neuro‐inflammation and to provide neuro‐protection and neuro‐regeneration in EAE/MS and related neuroinflammatory diseases.