Drug Discovery for Heart Channelopathies
Creative Bioarray is committed to helping clients develop drugs for the treatment of heart channelopathies, including Long QT Syndrome (LQTS), Short QT Syndrome (SQTS), and more. We focus on the modulation of ion channels to develop drugs that restore normal heart rhythm.
Introduction
Heart channelopathies are a group of genetic disorders in which mutations in genes encoding the major ion channel subunits of cardiomyocytes lead to abnormal ion channel function. These mutations often result in different phenotypes, such as syncope, seizures, and arrhythmias, based on abnormalities induced by sodium currents and other ionic currents. Common clinical types include LQTS, SQTS, Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (PVT).
In the research of gene mutations encoding ion channel subunit units, more than 1500 gene mutations in at least 26 subtypes have been found. According to different mutation ion channels, heart channelopathies can be divided into sodium channel disease, potassium channel disease, calcium channel disease, chloride channel disease, etc. However, currently available treatment options are still limited. A better understanding of molecular principles will not only help increase the understanding of heart channelopathies, but also help develop new specific treatments for genes or mutations.
Fig. 1 Clinical phenotypes associated with mutations in Nav1.5 sodium channels. (Fonseca, 2018)
Drug Development for Heart Channelopathies
Mutations in several genes encoding ion channels, such as KCNQ1 (Kv7.1), KCNH2 (HERG), KCNJ2 (Kir2.1), KCNJ5 (Kir3.4), SCN5A (Nav1.5), and SCN4B (Nav2.4), have been proved to be related to the occurrence of heart channelopathies. Symptomatic treatment aims to restore normal heart rhythm. The application of β-receptor antagonists and corresponding ion channel blockers may be effective for some ion channel diseases. Drugs can inhibit the induction of ventricular tachycardia and ventricular fibrillation through different mechanisms, which can be used as adjuvant treatment measures for these diseases. In addition, supplementing the corresponding ions can also be an effective adjunctive therapy for heart channelopathies. Our drug development services include, but are not limited to:
- Analysis of genotype-phenotype relationships in heart channelopathies, including LQTS and PVT.
- In vitro characterization of variants. We help clients obtain pathogenic information on putative pathogenic variants identified by high-throughput sequencing platforms through high-throughput approaches based on heterologous systems. And, our robotic and automated pipelines allow for rapid electrophysiological characterization of multiple variants.
- Development of physiological cellular models that mimic the genetic background in which variants function.
- Development of ion channel blockers.
- Culture of patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and development of precision medicine strategies based on iPSC-CMs.
With a world-class technology platform and experienced scientists in the field of drug research and development, Creative Bioarray has the strength to provide clients with comprehensive drug discovery services for heart channelopathies. We are committed to developing gene- and mutation-specific drugs to accelerate advances in precision medicine. If you are interested in our services, please contact us for more details.
Reference
- Fonseca, D. J.; da Silva, M. J. V. Cardiac channelopathies: the role of sodium channel mutations. Revista Portuguesa de Cardiologia (English Edition), 2018, 37(2): 179-199.
