Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.

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Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis

Frontiers in Neurology ◽

10.3389/fneur.2018.00005 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 57

Author(s):

Elizabeth A. Mills ◽

Magdalena A. Ogrodnik ◽

Andrew Plave ◽

Yang Mao-Draayer

Keyword(s):

Multiple Sclerosis ◽

Mechanism Of Action ◽

Dimethyl Fumarate

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Faculty Opinions recommendation of Emerging understanding of the mechanism of action for dimethyl fumarate in the treatment of multiple sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732615801.793556745 ◽

2019 ◽

Author(s):

David Selwood

Keyword(s):

Multiple Sclerosis ◽

Mechanism Of Action ◽

Dimethyl Fumarate

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Hematological Alterations Related to Treatment with Teriflunomide and Dimethyl Fumarate in Multiple Sclerosis

NeuroSci ◽

10.3390/neurosci1010003 ◽

2020 ◽

Vol 1 (1) ◽

pp. 17-23

Author(s):

Daniel Apolinar García-Estévez

Keyword(s):

Multiple Sclerosis ◽

Mechanism Of Action ◽

Blood Cells ◽

White Blood Cells ◽

Dimethyl Fumarate ◽

Acquired Immunity ◽

First Year ◽

Inherent Safety ◽

Safety Risks ◽

Hematological Alterations

The exact mechanism of action of different modifying treatments in the evolutionary course of multiple sclerosis (MS) remains unknown, but it is assumed that they act upon the cells involved in acquired immunity. One effect of these treatments is the development of lymphopenia, which carries inherent safety risks. This study was conducted to understand the alterations that teriflunomide (TERI) and dimethyl fumarate (DMF) exert upon white blood cells in a series of patients with MS. This study included a total of 99 patients; 44 treated with DMF and 55 patients treated with TERI. Blood counts were evaluated at baseline and every 6 months in order to track the absolute leukocyte, lymphocyte, and neutrophil counts. Twelve months after starting treatment, we observed a significant decrease in leukocytes (21.1%), lymphocytes (39.1%), and neutrophils (10%) in the DMF group. In the TERI group, leukocytes decreased by 11.1%, lymphocytes by 8.1%, and neutrophils by 15.7%. Both TERI and DMF produced a significant decrease in leukocytes during the first year of treatment and this was mainly related with a decrease in neutrophils in the TERI group and a decrease in lymphocytes in the DMF group.

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