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Imbrici P, Liantonio A, Camerino GM, et al. Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery. Front Pharmacol. 2016;7:121doi: 10.3389/fphar.2016.00121.
Imbrici, P., Liantonio, A., Camerino, G. M., De Bellis, M., Camerino, C., Mele, A., Giustino, A., Pierno, S., De Luca, A., Tricarico, D., Desaphy, J. F., & Conte, D. (2016). Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery. Frontiers in pharmacology, 7121. https://doi.org/10.3389/fphar.2016.00121
Imbrici, Paola, et al. "Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery." Frontiers in pharmacology vol. 7 (2016): 121. doi: https://doi.org/10.3389/fphar.2016.00121
Imbrici P, Liantonio A, Camerino GM, De Bellis M, Camerino C, Mele A, Giustino A, Pierno S, De Luca A, Tricarico D, Desaphy JF, Conte D. Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery. Front Pharmacol. 2016 May 10;7:121. doi: 10.3389/fphar.2016.00121. eCollection 2016. PMID: 27242528; PMCID: PMC4861771.
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Front Pharmacol. 2016 May 10;7:121. doi: 10.3389/fphar.2016.00121. eCollection 2016.

Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery.

Frontiers in pharmacology

Paola Imbrici, Antonella Liantonio, Giulia M Camerino, Michela De Bellis, Claudia Camerino, Antonietta Mele, Arcangela Giustino, Sabata Pierno, Annamaria De Luca, Domenico Tricarico, Jean-Francois Desaphy, Diana Conte

Affiliations

  1. Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro" Bari, Italy.
  2. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro" Bari, Italy.
  3. Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro" Bari, Italy.

PMID: 27242528 PMCID: PMC4861771 DOI: 10.3389/fphar.2016.00121

Abstract

In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation, and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets.

Keywords: channelopathies; drug discovery and development; genetics; ion channels pharmacology; physiopathology

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