It may come as no surprise that researchers are looking at how to personalise therapies to treat diseases of one of the body’s most important organs, the heart, in an era of precision medicine. According to recent studies, different genetic variables may contribute to different heart failure pathways, opening the door for potentially adaptable treatments.
The research, which was released on August 4 in the journal Science, disproves the widely held notion that heart failure, a difficult-to-treat and frequently fatal condition, results from a common final pathway. It also identifies new potential therapeutic targets and targets for the creation of personalised medications.
The discovery is based on an examination of 880,000 single cardiac cells from 18 healthy and 61 failing human hearts by 53 scientists from across the world, including researchers from Brigham and Women’s Hospital and Harvard Medical School. The researchers concentrated on tissue from people who had dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM), two diseases that typically result in cardiac failure and a need for a heart transplant.
Single-nucleus RNA-sequencing (snRNAseq) analysis was used by the worldwide team to generate a genetic readout for each cell in the heart tissue, allowing them to identify cellular and molecular alterations in each cell type.
The scientists discovered 71 unique transcriptional states and 10 essential cell types, noting that individuals with DCM or ACM had elevated endothelial and immune cells and a deficiency in cardiomyocytes, the cells in charge of contracting the heart muscle. The researchers observed molecular and cellular variations as well as some common responses when comparing different hearts with mutations in certain disease genes, such as TTN, PKP2, and LMNA.
The research discovered that, on average, those with a mutant RBM20 gene had heart failure and required a transplant considerably sooner than those with other hereditary forms of DCM. This finding was corroborated by a cross-reference with patient medical data.
Other observations include the progressive replacement of muscle cells in the hearts of ACM patients by fat and connective tissue cells, particularly in the right ventricle.
The research’s central finding is that various genetic abnormalities cause unique—and occasionally shared—reactions that might result in cardiac failure. The authors concluded that genotypes activate extremely specific heart failure pathways since “this network provided remarkably high genotype prediction for each cardiac sample.”
According to co-author Christine Seidman, M.D., director of the Cardiovascular Genetics Center at Brigham and professor at Harvard, the analysis allowed the researchers to observe that cardiomyopathies don’t always activate the same pathogenic pathways.
The researchers came to the conclusion that more study is necessary to fully comprehend the molecular pathways behind cardiomyopathies across certain demographics, various heart regions, and early stages of disease.
The team posted their data set online in the hopes that others will use it to create fresh approaches to treating heart failure. The ultimate objective, according to the study’s authors, is to develop personalised, genotype-specific therapies for people with heart disease that may be more efficient and have fewer side effects than current treatments.
