Pharmacogenetic and pharmaco-miR biomarkers for tailoring and monitoring myasthenia gravis treatments

ABSTRACT

Introduction

Inter-individual variation in drug efficacy and tolerability in myasthenia gravis (MG), an autoimmune disorder mostly treated by chronic immunosuppression, highlights the need of specific, safe and tailored precision medicine approaches. By targeting the disease-effector molecules, biological drugs are the most promising therapeutic agents to treat MG. A number of pharmacogenetic biomarkers associated with response to immunosuppressive drugs in MG have been identified, and microRNAs (miRNAs) are emerging as reliable markers for predicting or monitoring treatment response in individual patients.

Areas covered

This review provides an overview of pharmacogenetic and pharmaco-miR biomarkers associated with immunosuppressive treatment response in MG and other autoimmune diseases, pointing out the need of pharmacogenetic/-miR profiling for the recently developed biological drugs as an important step toward precision medicine.

Expert opinion

Extension of pharmacogenetic and pharmaco-miR data, and their entry into the clinical practice, hold the promise to greatly revolutionize MG therapy with clinically relevant drugs, including conventional and biological drugs, or their combination. High-throughput technologies, covering DNA and RNA, have the potential to disclose valuable pharmacogenomic/-miRNomic profiles able to guide the choice of the different drugs in individual patients, or biomarker-defined patients’ subgroups, thus significantly improving MG treatment in a cost/effective manner.

KEYWORDS:

• Myasthenia gravis
• pharmacogenetics
• pharmaco-miRs

Article highlights

• Pharmacogenetic and pharmaco-miR biomarkers can guide the choice of individualized treatment with conventional and/or biological drugs in MG patients, eventually enhancing the therapeutic success and lowering the side effects.

• Biomarkers of drug efficacy identified in autoimmune diseases, that share treatments with MG, can be useful for driving future pharmacogenetic/epigenetic research in MG to extend the existing data.

• Next-generation sequencing approaches can improve unbiased biomarker identification and disclose combinations of genomic and pharmaco-miR biomarkers associated with drug efficacy and toxicity in MG.

• Increasing the knowledge on genetic and epigenetic variations associated with response to treatments in MG patients could lead to the adoption of personalized therapies into the clinical practice.

• Biological drugs promise to increase specificity, efficacy and safety of MG treatment, particularly if applied within personalized approaches based on patient-specific pharmacogenomics/epigenomics biomarkers.

Declaration of interest

Renato Mantegazza received compensation for participating on Advisory Boards in relation to MG clinical trial design, Congress participation and research support in the last 5 years from: Alexion Pharmaceuticals, ARGENX Pharma, and Biomarin. Paola Cavalcante received a grant and was supported by the Italian Ministry of Health (Grant No: GR-2013-02358564 and Annual research funding) in the last 5 years. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.