New Approach Advances Precision Medicine for Heart Condition

An innovative approach helped researchers analyze the role of protein-protein interactions (PPIs) in cases of hypertrophic cardiomyopathy (HCM), a discovery that could advance precision medicine treatments for the heart condition, according to a study published in Nature Communications.

HCM is a cardiovascular disease characterized by thickening of the left ventricle, known as the main squeezing chamber of the heart. HCM is known for causing sudden death in athletes but can occur in individuals of any age, typically without symptoms.

Although the condition is frequently discussed in the context of genetics, most patients with HCM don’t have a known genetic variant.

“While genes play a role in HCM, there is more information surrounding this condition that can’t be explained with genetics alone,” said corresponding author Bradley Maron, MD, a cardiologist in the Division of Cardiovascular Medicine at the Brigham.

“This raises the question of whether there are other important components of the disease. With this project, we aim to provide an expanded view of the pathobiology of HCM in a way that doesn’t hinge on understanding specific gene mutations.”

Researchers collected tissue from 18 HCM patients recently recruited to receive myectomies, surgical procedures involving the excision of a portion of the heart muscle wall. In order to identify individual PPIs among the HCM cohort, the team analyzed tissue contents using RNA-sequencing, a technique that allows researchers to identify patterns of where and when genes are active.

In a series of steps, researchers identified patient-specific PPIs corresponding to the unique biological characteristics of each patient’s disease profile. The team found that they could distinguish individualized protein networks in each patient in the HCM cohort.

“These findings represent a major step forward for precision medicine,” said Maron. “With the identification of patient-specific biological wiring maps, researchers may one day develop personalized treatments informed by patients’ protein networks.”

The study is unique in that researchers studied affected tissue collected directly from HCM patients, enabling a more robust, accurate way of studying patients’ pathobiology than has been performed previously. In the future, the team will aim to develop less invasive ways to perform this same test, whether through the collection of blood samples or through other biomarkers in the clinic.

Additionally, the team wants to apply this same approach to other diseases as well, potentially expanding the scope of precision medicine.

“This study illustrates the complexity of HCM but also offers a clearer path forward for understanding the disease pathobiology with the promise of opportunity for precision medicine in this disease,” said Maron.

As the healthcare industry continues to seek more personalized, targeted therapies for a range of conditions, researchers have increasingly focused on improving their understanding of diseases to pave the way for precision medicine treatments.

In January 2021, researchers from Mount Sinai detected three molecular subtypes of Alzheimer’s disease that could advance precision medicine therapies for the condition. The results could lead to the identification of biomarkers and clinical features in living patients associated with these molecular subtypes, as well as earlier diagnosis and intervention.

“Our systematic identification and characterization of the robust molecular subtypes of Alzheimer’s disease reveal many new signaling pathways dysregulated in Alzheimer’s and pinpoint new targets,” said Bin Zhang, PhD, the lead author of the study, Director of the Center for Transformative Disease Modeling, and Professor of Genetics and Genomic Sciences at the Icahn School of Medicine.

“These findings lay down a foundation for determining more effective biomarkers for early prediction of Alzheimer’s, studying causal mechanisms of Alzheimer’s, developing next-generation therapeutics for Alzheimer’s, and designing more effective and targeted clinical trials, ultimately leading to precision medicine for the disease.”