Long QT Syndrome (LQTS)
Long QT syndrome (LQTS) is characterized by a prolonged heart rate corrected QT interval and dangerous arrhythmias that may lead to syncope and death. Protheragen is specialized in research services for the development of therapeutics for rare cardiovascular diseases, including LQTS. We provide an all-inclusive approach starting from target identification to advanced therapeutic development.
Introduction to Long QT Syndrome (LQTS)
Congenital long QT syndrome (LQTS) is a genetic heart disorder associated with syncope and a risk for sudden cardiac death. The ECG records an elongated QT interval which is not due to structural heart diseases or any external factors such as certain medications. The occurrence of LQTS was estimated to be around 1:2500, the number has risen over the years. Due to the presence of genetic mutations, LQTS is further subdivided into 17 subtypes, with the most common being LQT1, LQT2, and LQT3.
Fig.1 Genotype-phenotype link for subtypes 1, 2, and 3. (Wilde, A. A. M., et al., 2022)Pathogenesis of Long QT Syndrome (LQTS)
The subtypes LQT1 and LQT2 are associated with loss of function mutations in the potassium channel genes KCNQ1 and KCNH2, respectively. These genes are responsible for producing the slow and rapid delayed rectifier currents, IKs and IKr, oxidized for whom decreased amplitudes result in longer lengths of QT interval. LQT3 is associated with gain of function mutations of the SCN5A gene, which encodes the fast inward cardiac sodium current (INa). The gain of function in this context relates to a greater amplitude of the late sodium inward current during the plateau phase which, also prolongs the action potential.
Fig.2 Pathophysiological mechanisms of LQTS and related arrhythmias. (Wilde, A. A. M., et al., 2022)Therapeutics Development for Long QT Syndrome (LQTS)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| LQT-1213 | A new serum glucocorticoid-regulated kinase 1 (SGK1) inhibits the root cause of QT prolongation. | SGK1 | NCT05906732 | Phase I/II |
| Lumacaftor | Significantly reduce QTc and affect intracellular traffic of mutated protein products. | CFTR | NCT04581408 | Phase II |
| Propranolol | Partially reduce QTc through the blockade of sodium inward current during the late phase. | β-adrenoceptors | NCT00588965 | N/A |
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 our in-depth research and development approaches, we guarantee that every project is not only scientifically accurate but is also at the pinnacle of modern advancements. Our skilled professionals are committed to offering sophisticated diagnostic development, novel therapeutic intervention, and precise disease model development services that mirror intricate cardiovascular diseases such as LQTS.
Therapeutic Development Services
Animal Model Development for LQTS
The use of animal models is fundamental in understanding LQTS pathology, as well as in evaluating possible treatment options. We offer a fully integrated animal model development serving clients wanting to study LQTS, which provides relevance platforms to LQTS for preclinical research and drug development.
In these models, various drugs known to prolong the QT interval are administered to animals.
- Methoxamine-sensitized model
- Erythromycin-induced model
- Veratridine-induced model
- Fluconazole-induced model
- Other models
Utilizing gene-editing techniques to generate animals with mutations in LQTS-related genes.
- KvLQT1-/- model
- minK-/- model
- Merg1+/- model
- Kir2.2-/- model
- AnkB-/- model
- Other models
Alongside offering therapeutic research services, Protheragen conducts a wide array of both pharmacokinetics and drug safety review services. These vital assessments enable the refinement of dosing paradigms, examination of possible toxicities, and, guarantee that new medications are efficacious and safe for use. Don't hesitate to reach out to us if you would like to learn more about what we can offer.
Reference
- Wilde, Arthur A M et al. "Diagnosis, management and therapeutic strategies for congenital long QT syndrome." Heart (British Cardiac Society) 108.5 (2022): 332-338.
For research use only, not for clinical use.