Researchers at the University of Maryland School of Medicine (UMSOM) have identified previously undiscovered genetic mutations that are responsible for infantile dilated cardiomyopathy, a rare condition that causes heart failure in young children. The findings were published in Circulation in April 2021, which reported how the researchers were able to apply medications to counteract the mutation’s effects on cardiac muscle cells produced from stem cells collected from patients. The researchers believe that their discovery could lead to the development of treatments for the condition that do not require heart transplant surgery, which is currently the standard treatment.
Description of Infantile Dilated Cardiomyopathy
Infantile dilated cardiomyopathy is a relatively rare disorder occurring in around 1 in 200,000 births, and often results in heart failure. The cause of the condition is generally unclear, however, babies born with it often have less effective cardiac contractions which lead to decreased quantities of blood being pumped around the body. This reduced pumping can result in heart failure and is responsible for approximately 50% of all pediatric heart failure cases.
Discovery of Genetic Mutations
Led by Professor Charles “Chaz” Hong, the team of researchers used stem cells removed from the heart tissue of a sample of patients with dilated cardiomyopathy. The stem cells were converted into heart cells, which allowed them to study and manipulate them in laboratory conditions. After careful analysis, the team identified a genetic mutation responsible for the condition. This mutation often causes a protein that is found in a cell structure called the centrosome to malfunction. The centrosome is responsible for attaching to cells and providing a tether for the cell’s skeleton. When this protein malfunctions, the cells function less efficiently, and the muscle cells of the heart fail to organize themselves effectively. This leads to ineffective cardiac contractions, which eventually can result in heart failure.
Identifying Suitable Medication
The researchers discovered a drug that could improve symptoms associated with the disorder by improving the way muscle cells organize themselves. The medication used was C19, which helps to organize centrosomes in developing heart muscle cells derived from the patient’s stem cells. After treatment with C19, the patient’s heart muscle cells were restored to a more organized, efficient state, and their ability to contract was improved.
The Future of Dilated Cardiomyopathy Treatment
The researchers at the UMSOM are optimistic that their medical breakthrough could lead to better treatment for the often-fatal condition. Current treatments for dilated cardiomyopathy require a heart transplant, which is a difficult and dangerous procedure, especially for young children, making medical interventions, such as C19, a much less invasive option. Also, because the centrosomes play a fundamental role in heart muscle development, understanding this tissue-specific programmed process will be critical for future cardiac regenerative therapy efforts and may lead to improved outcomes.
Conclusions
The research undertaken by the team at the UMSOM stands out as an excellent example of how using cell manipulation techniques can lead to significant medical discoveries. There is hope that more studies will follow, which will confirm and clarify these findings, and in the future, more effective treatments can be developed, leading to improved health outcomes for those with infantile dilated cardiomyopathy.
