title: What's new about oral treatments in Multiple Sclerosis? Immunogenetics still under question.
abstract: Multiple Sclerosis (MS) is a chronic pathology affecting the Central Nervous System characterized by inflammatory processes that lead to demyelination and neurodegeneration. In MS treatment, disease modifying therapies (DMTs) are essential to reduce disease progression by suppressing the inflammatory response responsible for promoting lesion formation. Recently, in addition to the classical injectable DMTs like Interferons and Glatiramer acetate, new orally administered drugs have been approved for MS therapy: dimethyl fumarate, teriflunomide and fingolimod. These drugs act with different mechanisms on the immune system, in order to suppress the harmful inflammatory process. An additional layer of complexity is introduced by the influence of polymorphic gene variants in the Human Leukocyte Antigen region on the risk of developing MS and its progression. To date, pharmacogenomic studies have mainly focused on the patient's response following admission of injectable drugs. Therefore, greater consideration must be made to pharmacogenomics with a view to developing more effective and personalized therapies. This review aims to shed light on the mechanism of action of the new oral drugs dimethyl fumarate, teriflunomide and fingolimod, taking into account both the importance of immunogenetics in drug response and pharmacogenomic studies.
authors.affiliation: Laboratory of Immunogenetics, Department of Biology & Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy. Electronic address: cristiana.pistono01@ateneopv.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pistono
authors.affiliation: Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy. Electronic address: cecilia.osera@unipv.it.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Osera
authors.affiliation: Laboratory of Immunogenetics, Department of Biology & Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Boiocchi
authors.affiliation: Inter-Department Multiple Sclerosis Research Centre, National Neurological Institute "C. Mondino", Pavia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Mallucci
authors.affiliation: Laboratory of Immunogenetics, Department of Biology & Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
authors.forename: Mariaclara
authors.initials: M
authors.lastname: Cuccia
authors.affiliation: Inter-Department Multiple Sclerosis Research Centre, National Neurological Institute "C. Mondino", Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.affiliation: Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pascale
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003437:Crotonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069462:Dimethyl Fumarate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006885:Hydroxybutyrates; D007125:Immunogenetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D009570:Nitriles; D014052:Toluidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D003437:Crotonates; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride
keywords: Dimethyl fumarate; Dimethyl fumarate (PubChem CID: 637568); Fingolimod; Glatiramer acetate (PubChem CID: 3081884); Immunogenetics; Multiple sclerosis; Teriflunomide; fingolimod (PubChem CID: 107970); teriflunomide (PubChem CID: 54684141)