Andersen-Tawil Syndrome (ATS)
Facial and limb dysmorphisms, executive function difficulties, cardiac arrhythmia, and dominant KCNJ2 potassium channel mutations, represent the most defining characteristics of Andersen-Tawil syndrome (ATS), one of the periodic paralyses. At Protheragen, we offer end-to-end ATS research services about rare diseases of the heart. We recognize the multifactorial nature of the conditions and are devoted to making a difference in drug discovery and development.
Introduction to Andersen-Tawil Syndrome (ATS)
The dysfunction of inward rectifier potassium channels gives rise to Andersen-Tawil syndrome (ATS), which is a multisystem disorder characterized by episodic weakness, cardiac arrhythmias, dysmorphic features, and a unique neurocognitive profile. The onset is characteristically noticed during childhood or adolescence (averagely between 2-18 years) and is the rarest form of periodic paralysis with an ultra-low prevalence of around 1 in 500,000 to 1,000,000 individuals.
Fig.1 Cardiac feature of ATS. (Vivekanandam, V., et al., 2022)Pathogenesis of Andersen-Tawil Syndrome (ATS)
Andersen-Tawil syndrome (ATS) is a sporadic multisystem disorder characterized as a rare genetic channelopathy without structural heart disease (with some exceptions). ATS type 1 develops due to the mutations of the KCNJ2 gene, which encodes for the α subunit of the K+ channel protein Kir2.1. ATS type 2 is associated with the mutation on the KCNJ5-GIRK4 gene, which encodes for the G protein-sensitive-activated inwardly rectifying K+ ion channel Kir3.4 (15%), which conducts the acetylcholine-activated potassium current.
Fig.2 ATS related Kir2.1 mutation. (Handklo-Jamal, R., et al., 2020)Therapeutics Development for Andersen-Tawil Syndrome (ATS)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Acetazolamide | Possibly normalizing deviant ion channel function. | CAs | NCT00839501 | Phase I |
| Flecainide | Its potent inhibition of the NaV1.5 sodium channel slows conduction in cardiac tissue and extends refractory periods. | NaV1.5 | NCT06205550 | Phase II |
| Ranolazine | Lessen inducibility of ventricular tachycardias as well as premature ventricular activities. | NaV1.5 | / | Preclinical |
| Tetrodotoxin | Reduce the inducibility of ventricular tachycardias and premature ventricular activities without reducing conduction velocity. | NaV1.1 | / | 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
The integrated service system of our company incorporates everything from pioneering platforms for developing diagnostics to modern therapeutic methods. We can develop strong models for diseases that allow us to comprehend intricate pathologies, leading to precise therapeutics. Each of our comprehensive evaluations guarantees that every drug candidate surpasses established benchmarks, while our dedicated research teams apply novel techniques to analyze pharmacokinetics, complemented by our stringent safety assessments.
Therapeutic Development Services
Animal Model Development for ATS
ATS animal model development services are provided by our company to expedite drug discovery and development, as animal models are crucial in understanding the complex pathophysiology of ATS while also aiding in the refinement of therapy methods.
For the ATS chemical-induced animal models, chemicals or drugs are administered to reproduce symptoms resembling that of the syndrome.
Optional models: BaCl2/extracellular K+-induced model, cesium chloride-induced model, other models.
Genetically Engineered Animal Model
Using methods such as transgenesis or gene editing, tailored changes can be made to an organism's genome, resulting in genetically engineered models.
Optional models: Kcnj2 conditional knockout model, other models
Protheragen harnesses innovation and collaboration to propel progress. We strive to forge meaningful relationships with our clients so that, together, we can hasten the advent of new therapies. We have a thorough understanding of rare cardiovascular diseases such as ATS, and we offer a complete, fully integrated set of solutions tailored to the particular challenges posed by drug discovery and development. Should you be interested in our services, do not hesitate to get in touch with us.
References
- Handklo-Jamal, Reem et al. "Andersen-Tawil Syndrome Is Associated with Impaired PIP2 Regulation of the Potassium Channel Kir2.1." Frontiers in pharmacology 11 (2020): 672.
- Vivekanandam, Vinojini et al. "Andersen-Tawil syndrome: deep phenotyping reveals significant cardiac and neuromuscular morbidity." Brain: a journal of neurology 145.6 (2022): 2108-2120.
For research use only, not for clinical use.