Lovastatin in combination with metformin provides neuroprotection in experimental animal model of multiple sclerosis (P5195)
Abstract
Abstract Studies from our laboratory have previously reported that modulation of AMPK by metformin and isoprenylation of RhoA GTPase by statins attenuate inflammatory and autoimmune responses. Here, we evaluated the therapeutic efficacy of these drugs in combination to protect CNS in EAE, animal model of MS. Metformin and lovastatin are neuroprotective per se. Combination therapy using the suboptimal dose of the drugs following EAE induction provided synergistic effects in neuroprotection. Mechanistically, the neuroprotection offered was primarily through decreased infiltration of the immune cell (CD4, CD8 and CD68) and decreased axonal degeneration. Combination therapy also inhibited the EAE induced demyelination (LFB and MBP staining). The shattered homeostasis of phosphorylated form of neurofilament binding protein (SMI-31) during the EAE pathology was reverted back with the drug treatment. Further, CNPase, the marker of myelinating oligodendrotyes was increased by the metformin and lovastatin treatment. Combination treatment with lovastatin and metformin biased the class of elicited myelin basic protein antibody from IgG2a to IgG1 and IgG2b, suggesting a shift from Th1 to Th2 response. In summary, metformin and lovastatin treatment individually as well as in combination combats EAE disease. Since, metformin and lovastatin are FDA approved drugs; the present study suggests for a possible therapeutic application of their combination treatment for MS.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.