Jervell and Lange-Nielsen Syndrome (JLNS)

Jervell and Lange-Nielsen syndrome (JLNS) is a congenital disease that is passed down in an autosomal recessive pattern. This syndrome in particular results from deletion mutations in the KCNQ1 (90%) and KCNE1 genes which contain the necessary information for the protein constituents of the potassium channels in the heart and cochlea. Protheragen is a research service provider with a focus on one-stop drug discovery and development for JLNS. We will meet your every need with unrivaled services tailored specifically for these rare syndromes with the help of our expert team dedicated to achieving your therapeutic goals.

Introduction to Jervell and Lange-Nielsen Syndrome (JLNS)

Jervell and Lange-Nielsen syndrome (JLNS) describes the condition with profound bilateral sensorineural hearing loss at birth and long QT interval (usually >500 msec). An increase in QTc interval is associated with tachyarrhythmias such as ventricular tachycardia and may lead to torsade de pointes ventricular tachycardia, ventricular fibrillation, syncope, or sudden death. Also common in JLNS are iron-deficient anemia and high gastrin levels. The prevalence of the disorder is around 1 to 6 in 1,000,000 population.

FFig.1 The amino acid changes in KCNQ1. (Zhao, N., et al., 2023)

Pathogenesis of Jervell and Lange-Nielsen Syndrome (JLNS)

The cardiac action potential includes depolarization, plateau/refractory state, and rapid repolarization. The QTc interval represents the repolarization phase on an ECG. Repolarization is associated with the outflow of potassium from the cardiac cell via potassium permeability increase.

This type of current which is responsible for repolarization, known as the delayed outward rectifier current, consists of rapidly activating and slowly activating components. The alpha and beta subunits of the sluggishly activating components are encoded due to mutations in KCNQ1 and KCNE1 genes, which extend the QTc interval due to a slower movement of potassium outside the cell.

Fig.2 Family history of JLNS individuals. (Matsuda, S., et al., 2020)

Therapeutics Development for Jervell and Lange-Nielsen Syndrome (JLNS)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.

Our Services

Protheragen provides an all-inclusive approach that encompasses every detail of the drug development process starting from sophisticated diagnostic development, cutting-edge therapeutic technologies, and establishing reliable disease models. Our services are devised to close the gap between idea innovations and practical implementations so that your research is advanced with certainty.

Therapeutic Development Services

Diverse Platforms

• Small Molecule Drug Development
• Gene Therapy Development
• Therapeutic Peptide Development

• Cell Therapy Development
• Therapeutic Antibody Development
• Therapeutic Protein Development

Animal Model Development for JLNS

Through animal models, one can gain perspective on the structure and effects of the gene mutations that cause JLNS, in addition to being able to formulate and evaluate new therapies for this rare, yet grave disease. We can tailor pertinent animal models to your research specifications.

Genetically Engineered Animal Models

The established animal models for JLNS focus on manipulating KCNQ1 or KCNE1 genes to recapitulate the syndrome's key features.

• Kcne1^-/- model
• Other models

• Kcnq1^-/- model

Beyond the construction of both specific and custom animal models, Protheragen's platform offers advanced technique support for preclinical work including in-depth pharmacokinetics, detailed safety assessments, and many other support features. This conforms to our unwavering dedication to quality. Feel free to reach out to us at any time if you require further information on our available services.

References

• Matsuda, Shinichi et al. "Jervell and Lange-Nielsen syndrome with novel KCNQ1 and additional gene mutations." Human genome variation 7 (2020): 34.
• Zhao, Nongnong et al. "Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome." BMC cardiovascular disorders 23.1 (2023): 399.