Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

María José Zarzuelo Romero, Cristina Pérez Ramírez, María Isabel Carrasco Campos, Almudena Sánchez Martín, Miguel Ángel Calleja Hernández, María Carmen Ramírez Tortosa, Alberto Jiménez Morales, María José Zarzuelo Romero, Cristina Pérez Ramírez, María Isabel Carrasco Campos, Almudena Sánchez Martín, Miguel Ángel Calleja Hernández, María Carmen Ramírez Tortosa, Alberto Jiménez Morales

Abstract

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.

Keywords: alemtuzumab; cladribine; dimethyl fumarate; fingolimod; multiple sclerosis; natalizumab; ocrelizumab; polymorphisms; response; siponimod; teriflunomide.

Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported, and that there are no competing financial interests in relation to the work described in this article.

Figures

Figure 1
Figure 1
Mechanism of action of dimethyl fumarate.
Figure 2
Figure 2
Mechanism of action of teriflunomide.
Figure 3
Figure 3
Mechanism of action of natalizumab.
Figure 4
Figure 4
Mechanism of action of fingolimod.
Figure 5
Figure 5
Mechanism of action of alemtuzumab.
Figure 6
Figure 6
Mechanism of action of cladribine; DCK: Deoxycitidine Kinase.
Figure 7
Figure 7
Mechanism of action of siponimod.
Figure 8
Figure 8
Mechanism of action of ocrelizumab.

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