Accelerating research, improving care: Additional Ventures funds high-impact grants in single ventricle heart defects through MCHRI
March 1, 2021
By Roxanna Van Norman
Single ventricle (SV) heart defects are rare and affect about five in 100,000 newborns each year. This type of congenital heart defect occurs during the first eight weeks of pregnancy when one of the heart ventricles - the left and right lower chambers of the heart - does not form properly and is either too small or underdeveloped.
“Normally, we all have two ventricles, and one pumps to the body and the other pumps to the lungs, but single ventricle patients only have one functioning ventricle,” says Alison Marsden, PhD, Associate Professor of Pediatric Cardiology and Bioengineering at Stanford School of Medicine. “In patients with a single ventricle, that one ventricle has to do the work of both functioning chambers to pump blood to the body.”
Dr. Marsden is one of the recipients of a seed grant from Additional Ventures through Stanford Maternal and Child Health Research Institute (MCHRI). Launched in early 2020, MCHRI’s Additional Ventures Innovation Fund Single Ventricle Disease Research Awards Program provides seed grants to Stanford investigators for innovative, high-impact studies to treat and develop functional cures for SV heart defects. Dr. Marsden received the award in 2020 for her project to develop a mechanical device to induce ventricular growth in SV patients.
Single ventricle heart defects are highly complex, Dr. Marsden says. It leaves the baby with only one pumping heart chamber, leading to inefficient blood circulation and one ventricle that is overworked. Current solutions for this condition require a series of operations to ensure the one chamber can pump all of the blood throughout the body and provide enough oxygen to the child.
High-impact studies targeting SV heart defects
To address the gaps and challenges in treating SV defects, Stanford scientists have banded together in several multi-disciplinary collaborations.
That's one of the things I love most about Stanford is that as a basic scientist, this field got me interested in how arteries and veins come about in single ventricle disease.
“That's one of the things I love most about Stanford is that as a basic scientist, this field got me interested in how arteries and veins come about in single ventricle disease,” says Kyle Loh, PhD, Assistant Professor in the Department of Developmental Biology and 2020 recipient of the seed grant.
His background in developmental biology coupled with the expertise of Professor of Pediatric Cardiology Marlene Rabinovitch, MD, who specializes in SV heart defects, made for an ideal team to conduct research in this area, says Dr. Loh. The team is using stem cells to investigate the mechanism of lymphatic, arterial, and venous dysfunction in SV heart defects.
Thanks to the generous support from Additional Ventures, Stanford is one of five partner institutions to receive funding in a coordinated research initiative to drive scientific discoveries and development of treatments for SV heart defects. To date, MCHRI has awarded $692,000 to four research projects through this funding mechanism. The duration of funding for each project is 12 to 24 months.
The following are funded SV projects and their research updates during the first six months of the project:
- Mapping the Regulatory Wiring of Heart Development to Identify the Genetic Etiology of SV Defects
Genetic variation plays a vital role in the makeup of SV heart defects and may provide insights into heart development and defects. Jesse Engreitz, PhD, Assistant Professor in the Department of Genetics, is leading a project to understand the genetic underpinnings that lead to SV heart defects. This project involves the collective expertise of Sean Wu, MD, PhD, Associate Professor of Cardiovascular Medicine, William Goodyear, MD, PhD, Instructor in Pediatric Cardiology, Sharon Paige, MD, PhD, and James Priest, MD. Learn more.
- Understanding Arterial, Vein and Lymphatic Circulatory Dysfunction in Single Ventricle Disease Using Human Stem Cells
Patients with SV heart disease often develop long-term circulatory complications after undergoing several open-heart surgeries to reroute the blood network. What remains unknown is which blood vessels in the circulatory system - the arteries, veins, and lymphatics - influence the abnormalities associated with SV heart disease. Kyle Loh, PhD, Assistant Professor in the Department of Developmental Biology, is leading a project with co-investigator Marlene Rabinovitch, MD, Professor of Pediatric Cardiology, to understand the mechanism of the lymphatic, arterial, and venous dysfunction in SV heart disease. Learn more.
- Device for Mechanically Induced Ventricular Growth in Single Ventricle Patients
Current treatment for SV patients focuses on maintaining the health and performance of the one ventricle. Alison Marsden, PhD, Associate Professor in the Departments of Pediatrics and Bioengineering, wants to redirect the focus to technologies aimed at regrowing or salvaging whatever tissue exists of the second ventricle and develop a novel device to induce tissue growth in SV patients. The co-investigators on the project are Ellen Kuhl, PhD, Professor and Chair of Mechanical Engineering, Mark Cutkosky, PhD, Professor of Mechanical Engineering, and Daniel Bernstein, MD, Professor of Pediatric Cardiology. Learn more.
- A 3D Printed Vascularized Cardiac Biopump to Assist the Fontan Circulation
Newborns born with an SV often receive a series of operating procedures within the first two to three years, resulting in a Fontan circulation to help with blood flow. However, the Fontan procedure exerts pressure on the functioning ventricle, leading to cardiac complications. Mark Skylar-Scott, PhD, Assistant Professor of Bioengineering, and Frank Hanley, MD, Professor of Pediatric Cardiac Surgery, are leading a project to create a 3D-printed vascularized cardiac biopump to assist in the Fontan circulation.
To read highlights of awardees, click on the capsules below.
Roxanna Van Norman is the marketing manager for the Stanford Maternal and Child Health Research Institute.