Hypoplastic Left Heart Syndrome (HLHS)

Hypoplastic left heart syndrome (HLHS) is a critical form of congenital heart disease consisting of a combination of anatomical and functional deficiency of the left heart, with no viability for left ventricular support of systemic perfusion. Protheragen is a leading research service provider that provides one-stop comprehensive drug discovery and development services for HLHS and other rare cardiovascular diseases.

Introduction to Hypoplastic Left Heart Syndrome (HLHS)

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart defect that represents 30% of all infant deaths attributable to congenital heart disease. It is defined by hypoplasia of the left heart structures, i.e., aorta (Ao), aortic and mitral valves, and left ventricle. HLHS occurs in one of 3,841 live births and is responsible for almost 25% of total deaths within the first postnatal year.

Fig.1 Morphological contrasts of normal and HLHS hearts. (Bejjani, A. T., et al., 2021)

Pathogenesis of Hypoplastic Left Heart Syndrome (HLHS)

HLHS is the result of genetic mutations, abnormal mechanical stimuli, and defective cell signaling. HLHS is known as genetically heterogeneous and is predominantly represented by complex non-Mendelian genetics. Accordingly, mutations in GJA1, MYH6, NKX2-5, NOTCH1, ERBB4, ZIC3, RBFOX2, and HAND1 have been implicated as the cause of HLHS or closely related left ventricular outflow obstructive lesions (LVOTO). HLHS has also been described with some syndromic conditions, such as Turner syndrome, Jacobsen syndrome, trisomy 13, and trisomy 18.

Fig.2 HLHS characteristic endocardial abnormalities. (Datta, S., et al., 2023)

Therapeutics Development for Hypoplastic Left Heart Syndrome (HLHS)

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

Dedicated to excellence and innovation, we provide our partners with custom solutions to meet the challenges of rare cardiovascular diseases. Our collaborative team is committed to precision at every level, from molecular target discovery to preclinical validation, to help fast-forward promising drugs from the lab to the applications. We apply modern technology to provide state-of-the-art diagnostics, as well as new and improved therapeutic approaches, and strong disease models.

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 HLHS

Animal models are essential to our ability to progress with the study of HLHS and to assess new therapies. We are a full-service provider of customized animal model development services for high-fidelity models mimicking the HLHS phenotype, resulting in more rapid translation from discovery to application.

Genetically Engineered Model

Genetically engineered animal models are constructed through targeted cardiac-specific gene manipulations that can mimic developmental anomalies in the left heart.

• Ohia mutation model
• Sap130/Pcdha9 knockout model
• Other models

Surgical Animal Model

The animal models are created surgically to emulate obstructions or alterations in cardiac anatomy, which cause the underdevelopment of the left ventricle.

• Left atrial ligation (LAL) model
• Embolizing agent-induced model
• Other models

Protheragen prides itself on diligent preclinical research and rich experience in pharmacokinetics and safety evaluation. With our cutting-edge facilities, leading scientists, and excellence in quality, we are your most reliable partner in unlocking the potential of new therapies. Contact us if you would like to subscribe to our services.

References

• Bejjani, Anthony T et al. "Hypoplastic left heart syndrome (HLHS): molecular pathogenesis and emerging drug targets for cardiac repair and regeneration." Expert opinion on therapeutic targets 25.8 (2021): 621-632.
• Datta, Sayantap et al. "Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead." International journal of molecular sciences 24.20 (2023): 15249.