Therapies for Congenital Heart Defects

Translational medicine for hypoplastic left heart syndrome

Technology Overview

Dr. Vishal NigamDr. Vishal Nigam is a physician scientist in the field of pediatric cardiology – a field that is underserved by translational medicine. His research focuses on bringing new therapies from the bench to bedside for hypoplastic left heart syndrome (HLHS). HLHS is a congenital heart defect that results in underdeveloped structures of the left side of the heart. HLHS is a very serious condition, requiring multiple surgeries within the first months of life and many cardiac treatments over the patient’s lifetime, including an eventual heart transplant. Even with those treatments, HLHS patients have only 60-70% five-year survival.

Dr. Nigam is focused on answering fundamental questions about HLHS and translating that knowledge directly into new therapies. One area of research involves the identification of abnormal biomechanical stimuli in utero that can lead to HLHS. Dr. Nigam has recently developed a computer model that indicates that reduced ventricular filling leads to reduced ventricular growth due to decreased biomechanical stimuli. This model could be used to predict the extent of hypoplasia and provide guidance for treatment.

Dr. Nigam is working to determine how to grow the left ventricle of HLHS patients. In collaboration with engineers at the University of Washington, he is developing new shunts and medical devices for HLHS. He is also working on new animal models for cardiomyocyte development under biomechanical pressure. Further, during the surgeries that are necessary for HLHS treatment, use of heart-lung machines results in a severe inflammatory response. Dr. Nigam is working to develop anti-inflammatory drugs and miRNAs to modulate the inflammatory response.

Dr. Nigam is interested in working with industry partners to help develop new treatments for HLHS. He is interested in developing novel shunts and other medical devices, and testing new anti-inflammatory drugs or miRNAs during HLHS surgeries. In the future, Dr. Nigam’s research has the potential to utilize translational medicine to improve outcomes for HLHS patients.

Stage of Development

• Pre-clinical in vivo
• Pre-clinical in vitro

Partnering Opportunities

• Collaborative research and development opportunity
• Sponsored research agreement
• Tissue sample access

Publication

1. Dewan S, Krishnamurthy A, Kole D, …. Nigam V, McCulloch AD. Model of human fetal growth in hypoplastic left heart syndrome: Reduced ventricular growth due to decreased ventricular filling and altered shape. Front Pediatr. 2017; 5:25.
2. Patel V, Carrion K, Hollands A, …. Nigam V. The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells. FASEB J. 2015; 29: 1859-68.
3. Banerjee I, Carrion K, Serrano R, …. Nigam V. Cyclic stretch of embryonic cardiomyocytes increases proliferation, growth, and expression while repressing Tgf-β signaling. J Mol Cell Cardiol. 2015; 79: 133-44.
4. Carrion K, Dyo J, Patel V, Sasik R, …. Nigam V. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS One. 2014; 9: e96577.

Learn More

• Vishal Nigam, MD