Metformin for treatment of multiple sclerosis?

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jackD
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Metformin for treatment of multiple sclerosis?

Post by jackD » Tue Feb 03, 2015 8:55 pm

Seems like Metformin does all the right things to treat MS.

jackD

J Immunol. 2009 Jun 15;182(12):8005-14. doi: 10.4049/jimmunol.0803563.

Metformin attenuated the autoimmune disease of the central nervous system in animal models of multiple sclerosis.

Nath N, Khan M, Paintlia MK, Singh I, Hoda MN, Giri S

J Immunol. 2009 Sep 1;183(5):3551. Singh, Inderjit [added].

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the CNS. Metformin is the most widely used drug for diabetes and mediates its action via activating AMP-activated protein kinase (AMPK). We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES). Furthermore, the AMPK activity and lipids alterations (total phospholipids and in free fatty acids) were restored by metformin treatment in the CNS of treated EAE animals, suggesting the possible involvement of AMPK. Metformin activated AMPK in macrophages and thereby inhibited biosynthesis of phospholipids as well as neutral lipids and also down-regulated the expression of endotoxin (LPS)-induced proinflammatory cytokines and their mediators (iNOS and cyclooxygenase 2). It also attenuated IFN-gamma and IL-17-induced iNOS and cyclooxygenase 2 expression in RAW267.4 cells, further supporting its anti-inflammatory property. Metformin inhibited T cell-mediated immune responses including Ag-specific recall responses and production of Th1 or Th17 cytokines, while it induced the generation of IL-10 in spleen cells of treated EAE animals. Altogether these findings reveal that metformin may have a possible therapeutic value for the treatment of multiple sclerosis and other inflammatory diseases.


PMID: 19494326 [PubMed - indexed for MEDLINE] PMCID: PMC2965405

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NHE
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Re: Metformin for treatment of multiple sclerosis?

Post by NHE » Wed Feb 04, 2015 3:19 am

jackD wrote:Seems like Metformin does all the right things to treat MS.
Metformin blocks the absorption of vitamin B12. A B12 deficiency can cause demyelination of the spinal cord (known as subacute combined degeneration) and also periventricular brain lesions that mimic MS. Anyone taking metformin should get their B12 levels checked periodically and also consider using a sublingual methylcobalamin supplement.

http://www.medscape.com/viewarticle/719043

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Petr75
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Re: Metformin for treatment of multiple sclerosis?

Post by Petr75 » Sat Sep 19, 2020 12:37 pm

2020 Aug 19
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Poland
Metformin as a Potential Agent in the Treatment of Multiple Sclerosis
https://pubmed.ncbi.nlm.nih.gov/32825027/

Abstract

Metformin, a synthetic derivative of guanidine, is commonly used as an oral antidiabetic agent and is considered a multi-vector application agent in the treatment of other inflammatory diseases. Recent studies have confirmed the beneficial effect of metformin on immune cells, with special emphasis on immunological mechanisms. Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by various clinical courses. Although the pathophysiology of MS remains unknown, it is most likely a combination of disturbances of the immune system and biochemical pathways with a disruption of blood-brain barrier (BBB), and it is strictly related to injury of intracerebral blood vessels. Metformin has properties which are greatly desirable for MS therapy, including antioxidant, anti-inflammatory or antiplatelet functions. The latest reports relating to the cardiovascular disease confirm an increased risk of ischemic events in MS patients, which are directly associated with a coagulation cascade and an elevated pro-thrombotic platelet function. Hence, this review examines the potential favourable effects of metformin in the course of MS, its role in preventing inflammation and endothelial dysfunction, as well as its potential antiplatelet role.
https://www.eboro.cz/ms/

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Petr75
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Re: Metformin for treatment of multiple sclerosis?

Post by Petr75 » Tue Mar 16, 2021 12:13 pm

2021 Apr
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Metformin Protects Myelin from Degeneration in A Mouse Model of Iysophosphatidylcholine-Induced Demyelination in The Optic Chiasm
https://pubmed.ncbi.nlm.nih.gov/33650828/

Abstract

Objective: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. The autoimmune pathology and long-term inflammation lead to substantial demyelination. These events lead to a substantial loss of oligodendrocytes (OLs), which in a longer period, results in axonal loss and long-term disabilities. Neural cells protection approaches decelerate or inhibit the disease progress to avoid further disability. Previous studies showed that metformin has beneficial effects against neurodegenerative conditions. In this study, we examined possible protective effects of metformin on toxin-induced myelin destruction in adult mice brains.

Materials and methods: In this experimental study, lysophosphatidylcholine (LPC) was used to induce demyelination in mice optic chiasm. We examined the extent of demyelination at different time points post LPC injection using myelin staining and evaluated the severity of inflammation. Functional state of optic pathway was evaluated by visual evoked potential (VEP) recording.

Results: Metformin attenuated LPC-induced demyelination (P<0.05) and inflammation (P<0.05) and protected against significant decrease (P<0.05) in functional conductivity of optic tract. These data indicated that metformin administration attenuates the myelin degeneration following LPC injection which led to functional enhancement.

Conclusion: Our findings suggest metformin for combination therapy for patients suffering from the myelin degenerative diseases, especially multiple sclerosis; however, additional mechanistic studies are required.
https://www.eboro.cz/ms/

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Re: Metformin for treatment of multiple sclerosis?

Post by Petr75 » Tue Jun 15, 2021 10:16 am

2021 May 28
Department of Endocrinology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
Metformin Reverses Hashimoto's Thyroiditis by Regulating Key Immune Events
https://pubmed.ncbi.nlm.nih.gov/34124070/

Abstract

Background: Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.

Methods: This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing.

Findings: We found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment.

Interpretation: These experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.
https://www.eboro.cz/ms/

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