Ankyrin-B Syndrome
Ankyrin-B syndrome is an inherited cardiac arrhythmias (ICA) condition associated with sick sinus syndrome and cardiac conduction defect, which has symptoms such as syncope. Protheragen is an advanced research service provider pioneering integrated drug discovery and development services for rare cardiovascular conditions like Ankyrin-B syndrome. Through innovative research, our company works to develop novel therapies designed specifically for the difficulties associated with rare cardiovascular diseases
Introduction to Ankyrin-B Syndrome
Ankyrin-B syndrome which follows an autosomal dominant pattern of inheritance is a complex phenotype of the heart, including bradycardia and heart rate fluctuation, complete blockage of cardiac conduction, atrial fibrillation, prolongation of the QT interval, and possibly lethal catecholaminergic polymorphic ventricular tachycardia. When associated with prolonged QT interval, it is sometimes referred to as long QT syndrome type 4.
Fig.1 Echocardiography for individuals affected by Ankyrin-B syndrome. (Song, J., et al., 2022)Pathogenesis of Ankyrin-B Syndrome
Ankyrin-B is a multifunctional adapter protein encoded by ANK2, the expression and targeting of which are critical for the cardiac multifunctional adapter protein ion channels, transporters, cytoskeletal proteins, and signaling proteins involved. Variants of ANK2 in the unusual disorder known as Ankyrin-B syndrome led to the loss of function of the protein, which disrupts the normal regulation of sodium and calcium ions intracellularly, increasing the risk of arrhythmias, particularly torsades de pointes (TdP).
Fig.2 Representation of Ankyrin-B shows binding sites and protein domains. (Koenig, S. N., and Mohler, P. J., 2017)Therapeutics Development for Ankyrin-B Syndrome
| Drug Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|
| Metoprolol succinate | Targeted suppression of beta-1 adrenergic receptors results in diminished heart rate, myocardial contractility, and cardiac output. | β1-adrenergic receptor | Approved |
| AC3I | This is classified as a CaMKII inhibitor that can correct cardiac ryanodine receptor RyR2 dysregulation. | CaMKII | Preclinical |
| KN-93 | Correct anomalies in Ankyrin-B+/- myocyte electrical dysfunction including cellular afterdepolarizations, and significantly reduces cardiac arrhythmias in animal models. | CaMKII | Preclinical |
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
With a combination of scientific knowledge and innovative approaches, we have formed a multidisciplinary team of experts with extensive experience in cardiovascular research and drug development. This is achieved through a comprehensive services platform that encompasses services in diagnostics, therapeutics, and the development of disease models, thereby streamlining the process of developing therapeutics and enabling faster results.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for Ankyrin-B Syndrome
Protheragen provides custom development solutions tailored specifically towards Ankyrin-B syndrome since animal models are needed for the drug development stage as they comprehensively evaluate the mechanisms of the disease alongside the therapeutic benefits and effectiveness.
Genetically Engineered Animal Models
A genetically engineered mouse model expressing targeted mutations in a specific gene recapitulates the cardiac arrhythmias and neurological impairments observed in human Ankyrin-B syndrome.
Optional models:
- Ankyrin-B+/- model
- Other models
At Protheragen, we pride ourselves on an approach that incorporates all aspects of the preclinical research process. Our evaluation incorporates a comprehensive analysis of pharmacokinetics and drug safety assessment for therapeutic candidates to guarantee optimum efficacy and tolerability before human trial. For further inquiry, please reach out to us.
References
- Koenig, Sara N, and Peter J Mohler. "The evolving role of ankyrin-B in cardiovascular disease." Heart rhythm 14.12 (2017): 1884-1889.
- Song, Jin et al. "Ankyrin-2 genetic variants: A case of Ankyrin-B syndrome." Annals of noninvasive electrocardiology: the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 27.4 (2022): e12933.
For research use only, not for clinical use.