Atrial Septal Defect

Atrial septal defects result due to inadequate or absent tissue at the interatrial septum. If left untreated, individuals may suffer from volume overload in the right chambers of the heart, lead to irregular heartbeats in the atria, or develop high blood pressure in the lungs' arteries. Protheragen focuses on advancing therapy development for rare forms of cardiovascular diseases such as atrial septal defects which fuel their research services. With our unique experience and portfolio of preclinical research, we have established ourselves as a strong supporter of drug discovery and development services.

Introduction to Atrial Septal Defect

Atrial septal defects rank among the most frequently found congenital heart disease (CHD) occurring with an estimated prevalence of 56 to 100 per 100,000 live births. Exemplified as a simple defect, there are still great difficulties concerning the best diagnostic and therapy paths to take because of the varying anatomy and time-dependent complications involved. The three main types of atrial septal defects are ostium secundum defect, ostium primum defect, and sinus venosus.

Fig.1 Range of atrial septal defects. (Brida, M., et al., 2022)

Pathogenesis of Atrial Septal Defect

Although the majority of atrial septal defects manifest sporadically without a clear causative explanation, these abnormalities are sometimes noted within the context of genetic disorders including Down syndrome, Holt-Oram syndrome, and Noonan syndrome. Here, certain genes, including some mutations in the cardiac transcription factor gene NKX2-5, GATA4, TBX5, and others, have been correlated with atrial septal defects, as well. Furthermore, some correlating factors and conditions that increase the likelihood of having a child with atrial septal defects include the use of alcohol and tobacco, antidepressant drugs, and diabetes during pregnancy.

Fig.2 Types of atrial septal defects and their echocardiogram findings. (Brida, M., et al., 2022)

Therapeutics Development for Atrial Septal Defect

An atrial septal defect is often considered a subtype of congenital structural heart defect which was treated in the past using surgery or interventional devices. The latest research focusing on the atrial septal defect pharmacotherapy paradigm targets the relief of accompanying pathophysiological processes, for instance, providing sildenafil may relieve some cardiac workload which can slow down ventricular dysfunction progression and enhance cardiac performance.

Our Services

With a focus on innovations, our company offers a fully integrated service built around one-stop drug discovery and development, seamlessly combining modern diagnostic innovation with novel therapeutic approaches and sophisticated disease model development. Our multidisciplinary professionals tackle the intricacies of these diseases while catering to all their needs, where the processes are tailored uniquely for each project.

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 Atrial Septal Defect

Considering the great importance of animal models in atrial septal defect research, our company is focused on providing complete solutions for the development of atrial septal defect animal models by designing custom models optimized for translation to later-stage trials and offering frameworks designed with practical, testable hypotheses useful for evaluating new therapy methods at their initial development stages before human trials.

Genetically Engineered Models

Genetic modification of animals with transgenic or gene knockout techniques to alter specific genes to create genetically engineered models.

• TAMEK/MH double transgenic model
• NIPBL^+/- model
• Other models

Surgical Animal Models

Surgically induced models entail invasive surgical techniques to create an atrial septal defect and replicate the hemodynamic and structural changes seen in atrial septal defect individuals.

• Atrial septal puncture-induced model
• Other models

Alongside our integrated disease modeling, Protheragen also offers extensive preclinical services, including pharmacokinetic evaluation and safety profiling. This combination enables our collaborators to expedite the progression of innovative therapeutic candidates from the bench toward more advanced trials. Should our services be of interest, please get in touch with us.

Reference

• Brida, Margarita et al. "Atrial septal defect in adulthood: a new paradigm for congenital heart disease." European heart journal 43.28 (2022): 2660-2671.