Tetralogy of Fallot (TOF)
Tetralogy of Fallot (TOF) is a cyanotic congenital heart disease, which is a fusion of four defects; ventricular septal defect, stenosis of the pulmonary artery, overriding of the aorta, and hypertrophy of the right ventricle. Protheragen is one of the leading research service providers focusing on rare cardiovascular diseases, TOF. We provide an integrated, end-to-end service for the drug discovery and development of new drugs for these hard-to-treat diseases, uniquely tailored to meet the needs of clients.
Introduction to Tetralogy of Fallot (TOF)
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect, occurring in 3 per 10,000 live children and it represents 5-10 percent of all congenital heart lesions. The TOF heart anatomy allows for the mixing of blood between the pulmonary and systemic circulations. This combination most frequently occurs at the VSD, as the right-to-left shunt deposits deoxygenated blood into the systemic circuit, leading to cyanosis.
Fig.1 Characteristics of TOF. (Althali, N. J., and Hentges, K. E., 2022)Pathogenesis of Tetralogy of Fallot (TOF)
The causes and origins of TOF are not completely understood. Nevertheless, it has been known that genetic factors within chromosomes are part of the etiology. These genetic factors disrupt the signaling pathways that contribute to the growth of cardiac cells, and that in particular and most commonly affect those responsible for the interventricular septum. The pathways included GATA4, FTL4, and Slit-ROBO. Disruption of these pathways results in malformations of the RV outflow tract (RVOT), changes in angiogenesis, and migration and alignment of the cardiac cells.
Fig.2 The syndrome of cardiac dysfunction in repaired TOF. (Alipour Symakani, R. S., et al., 2023)Therapeutics Development for Tetralogy of Fallot (TOF)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Dapagliflozin | Modifying cardiac loading, improving myocardial energy metabolism, and minimizing oxidative stress. | SGLT2 | NCT06668389 | Phase IV |
| Dexmedetomidine | Reducing the afterload of the ventricles, Increases the cardiac output and consequently reduces myocardial injury. | α-2 adrenergic receptor | NCT05579964 | Phase II/III |
| Sacubitril/Valsartan | Act cooperatively to limit cardiomyocyte cell death and matrix remodeling. | AT1R, CD10 | NCT06693674 | Phase III |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Using the latest technology and a vast team of experts, we offer a complete solutions package, combining diagnostic development, therapeutic testing, and disease model development. Whether you need the latest biomarkers to detect the disease at its earliest stage or a complex model that mirrors the complicated pathophysiology associated with TOF, we guarantee that everything that your drug development program requires is carefully planned and delivered on time.
Therapeutic Development Services
Animal Model Development for TOF
Animal models allow the complex pathophysiological hallmarks of TOF to be reproduced with a degree of control to investigate disease development, genetics, and molecular mechanisms. Our company specializes in providing custom animal model development services for TOF study and reproducing some of the characteristics of TOF pathology.
TOF genetically engineered animal models involve targeted genetic modifications in animals to recapitulate the complex cardiac malformation and developmental defects present in the disease.
Optional models:
- Vegf120/120 mutant model
- other models
In addition to early discovery and development, Protheragen's services apply to key preclinical studies such as pharmacokinetic investigations and safety evaluations. Through a full-service offering, we enable our partners to bring innovative therapeutics to researchers with the confidence to support them through the preclinical development process. SERVICES Interested in our services, contact us.
References
- Althali, Nouf J, and Kathryn E Hentges. "Genetic insights into non-syndromic Tetralogy of Fallot." Frontiers in physiology 13 (2022): 1012665.
- Alipour Symakani, Rahi S et al. "The right ventricle in tetralogy of Fallot: adaptation to sequential loading." Frontiers in pediatrics 11 (2023): 1098248.
For research use only, not for clinical use.