In a promising development for pediatric cardiology, a University of Houston researcher has identified both a previously unknown cause and a potential in-utero treatment for left ventricular non-compaction (LVNC), commonly known as spongy heart disease — a serious congenital condition that frequently leads to heart failure and often necessitates a transplant early in life.
Medicine characterizes LVNC by an abnormal development of the heart’s left ventricle, resulting in a spongy, trabeculated muscle incapable of contracting and relaxing effectively to pump blood. It ranks among the most prevalent pediatric cardiomyopathies and presents significant risks of early heart failure in infants.
In research published in Circulation: Heart Failure, Mingfu Wu, professor of pharmacology and an expert in cardiac development at UH, and his team have shown that the dysfunction stems from a loss of activity in a group of proteins known as the Numb Family Proteins (NFPs). These proteins play a crucial role in the epicardium — the outer layer of the heart — where they facilitate essential communication between cell types during cardiac development. When this signaling is disrupted, fibroblasts fail to populate the trabeculae properly, leading to impaired structural formation in the ventricle, Wu explained.
“We found that the loss of function in certain proteins, called Numb Family Proteins … leads to non-compaction cardiomyopathy, presenting with pediatric-onset heart failure,” Wu said, outlining how disrupted fibroblast growth factor (Fgf) signaling lies at the heart of the condition.
Crucially, the research team’s experiments showed that supplementing Fgf signaling in utero — administering the growth factor to pregnant mothers — can partially restore normal heart development in animal models. This intervention enabled epicardial cells to enter the myocardium, reinstating fibroblast presence and improving trabecular support during a critical window before the coronary system forms.
“This impairment ultimately resulted in a spongy heart,” Wu noted. “When Fgf is given from outside the body to the pregnant mother, it can partially fix the problem, preventing a spongy heart.”
A new path forward
The findings signal a potential shift in how clinicians could approach LVNC. From postnatal management and transplant preparation to prevention during fetal development. By identifying the disrupted signaling pathway as a therapeutic target, Wu’s work lays the groundwork for future strategies that could intervene before birth and halt the progression of this debilitating disease.
In addition to illuminating the mechanism behind NFP-related LVNC, the study builds on Wu’s earlier research that linked the absence of the Itgb1 gene to improper ventricular compaction, underscoring the complex molecular choreography required for normal heart development.
While the therapeutic in-utero approach remains in early stages and requires further research before clinical application, experts say the discovery could have broader implications not only for congenital LVNC but also for adult cardiomyopathies rooted in epicardial dysfunction. Wu suggests that a deeper understanding of epicardial–myocardial crosstalk might yield novel treatments across a spectrum of heart diseases.
The University of Houston team’s research adds a new chapter to ongoing efforts to decode the fundamental biology of heart formation and opens avenues toward interventions that begin before birth, offering hope to families affected by one of the most challenging forms of pediatric heart failure.
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