<div style="text-align: justify; "><b style="font-size: 1rem;">Researchers at the University of Maryland School of Medicine (UMSOM) have discovered novel gene mutations responsible for a rare illness that causes heart failure in youngsters. They were subsequently able to discover how the mutation works and apply medication to counteract its effects in cardiac muscle cells produced from the patient's stem cells.</b><br></div><div style="text-align: justify;"><br></div><div style="text-align: justify;">The findings, published in late April in Circulation, suggest that treatments could be developed to manage the condition rather than requiring a heart transplant, which is the standard treatment for this condition in children.</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">"Although much has been studied about heart failure in adults, there is still much to learn about the genetic causes of heart failure in infants," said Charles "Chaz" Hong, MD, PhD, Melvin Sharoky, MD Professor of Medicine and Physiology, Director of Cardiology Research, and Co-Chief of Cardiovascular Medicine at UMSOM. "Mutations in the gene we identified had been implicated in microcephaly in babies but not yet in human heart disease."</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">Infantile dilated cardiomyopathy is a common cause of heart failure -- responsible for about half of pediatric heart failure cases -- whose cause is most often unknown. Although relatively rare, occurring in about one in 200,000 births, infants with the condition have hearts that fail to contract as effectively, so they are not able to pump as much blood as they should.</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">This genetic mutation discovered by Dr. Hong and his colleagues was found to normally make a protein found in a cell structure, the centrosome, that functions as a tether for the cell's skeleton and is best known for its role during cell division.</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">Without this protein, muscle cells in the heart were unable to organize themselves neatly and did not contract as well, which in turn affected the heart's pumping, the researchers theorized.</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">"We originally dismissed our findings as artifacts that the cell division machinery would be involved in this kind of heart muscle dysfunction," said Dr. Hong. "We thought that once the heart cells matured, this cell division machinery completely disappeared, but it turned out, it moves to a new location in the cell and takes on a new role in heart muscle function."</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">"This is the first human disease known to be caused by disrupting the transition in centrosome structure which normally occurs shortly after birth," said Matthew Miyamoto, the first co-author who worked on this project as a rising second-year medical student in Dr. Hong's laboratory.</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">The researchers then used the drug C19 that was known to organize centrosomes in developing heart muscle cells derived from the patient with infantile dilated cardiomyopathy. The drug restored organization of the developing heart muscle cells grown in a dish from the patient's stem cells and their ability to contract.</div><div style="text-align: justify;"><br></div><div style="text-align: justify;">"Because centrosomes play such a fundamental role in heart muscle development, specifically cell replication, structure, and function, a better understanding of this tissue-specific programmed process will be highly relevant to future cardiac regenerative therapy efforts," said UMSOM Dean, Mark T. Gladwin, MD, who is also Vice President for Medical Affairs, University of Maryland, Baltimore (UMB), and the John Z. and Akiko K. Bowers Distinguished Professor.Dr. Hong added, "It is only through collaborations between cardiologists, medical student trainees, and laboratory researchers that allowed this biomedical discovery which we hope will one day translate to medical treatments for children with this condition." HT</div><div style="text-align: justify;"><br></div><div style="text-align: justify; ">bnbd24/kh</div>