Developing new precision therapies for heart failure using both genomic and non-genomic approaches is the goal of an expanded research effort announced today by Bayer and The Broad Institute of MIT and Harvard.
Through the new Precision Cardiology Laboratory, Bayer and the Broad said, researchers aim to learn more about heart failure, then develop new treatments. The lab will initially use the Broad’s expertise in sequencing genetic information in individual cells from healthy and diseased hearts to develop high-resolution, single-cell maps of cardiovascular tissues in human and animal models.
Using tissue samples donated by healthy individuals as well as people with cardiovascular disease, researchers will build datasets to accelerate insights into heart failure, according to Bayer and the Broad.
"Such high-resolution maps of cells and tissues will be a profound asset for understanding heart failure and for developing new and better drugs," Patrick T. Ellinor, M.D., Ph.D., who will lead the Precision Cardiology Laboratory, said in a statement.
Dr. Ellinor is a cardiologist and an associate member of the Broad who is director of the Cardiac Arrhythmia Service at Massachusetts General Hospital (Mass General), and a professor of medicine at Harvard Medical School.
At the Broad, Dr. Ellinor’s lab seeks to apply genetics to understand the molecular basis of abnormalities of the heart rhythm and heart function.
“Our primary research focus has been on atrial fibrillation, a common arrhythmia affecting over 3 million Americans. To identify novel pathways for atrial fibrillation we are using a broad range of techniques including population genetics, cardiac electrophysiology, and animal models of arrhythmias,” Dr. Ellinor’s lab states on its website.
GWAS: 97 Loci Linked to AF
In his most recently published study, Dr. Ellinor led a research team that carried out what it said was the largest meta-analysis of genome-wide association studies (GWAS) for atrial fibrillation (AF) to date, consisting of more than half a million individuals, including 65,446 with AF. The team identified 97 loci significantly associated with atrial fibrillation, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis.
Dr. Ellinor and colleagues performed RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples to identify AF-associated genes at the GWAS loci. The researchers also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci, according to their study, “Multi-ethnic genome-wide association study for atrial fibrillation,” published June 11 in Nature Genetics.
“The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways,” Dr. Ellison and colleagues concluded. “These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.”
Bayer will contribute $22 million over the next five years to the Precision Cardiology Laboratory, which will consist of about 20 investigators. Their affiliations will be divided between the two organizations.
The $22 million is part of a total $100 million that Joerg Moeller, M.D., member of the Executive Committee of Bayer's Pharmaceuticals Division and head of research and development, told The Boston Globe Bayer has invested in what are now three collaborations with the institute.
The first collaboration began in 2013, when the Broad and Bayer launched an oncogenomics program to jointly discover and develop therapeutic agents that selectively target cancer genome alterations over five years. In 2015, the partners began a cardiovascular program designed to use genomics to better understand cardiovascular disease.
As with the earlier collaborations, Bayer and the Broad said, they will continue to openly share findings that arise from the Precision Cardiology Laboratory through both publicly-available datasets and academic journals.
“The Broad Institute is an important and strategic partner for Bayer enabling us to deepen our understanding in the area of cardiovascular diseases and we are looking forward to extending our collaboration even further,” Dr. Moeller stated.