Little (a), Big Risk: G3 Therapeutics Sets Out to Unravel Lp(a)-Driven Cardiovascular Disease (Lipoprotein(a)-Driven Cardiovascular Disease)

G3 is trailblazing the next frontier of cardiovascular disease

SAN FRANCISCO, Jan. 4, 2024 /PRNewswire/ -- G3 Therapeutics ("G3"), a global leader in the use of multiomic biological Big Data, has initiated a groundbreaking initiative to unravel the contribution of Lipoprotein(a) ["Lp(a)"] to cardiovascular disease (CVD). As the treatment of LDL cholesterol has resulted in dramatic improvements in cardiovascular health over the past couple of decades, Lp(a)-driven cardiovascular disease has emerged as the next frontier in cardiovascular medicine.

Elevated Lp(a) is the most prevalent genetically determined dyslipidemia and Lp(a)-driven cardiovascular disease may be the most prevalent form of genetically determined CVD. G3's visionary platform, spatial and longitudinal multiomics, anchored in genomics and coupled with deep, precision phenotyping of the cardiovascular system, provides a unique and unprecedented opportunity to unravel the biological mechanisms of Lp(a)-driven CVD. G3 will leverage its propriety data from its own GLOBAL clinical study (NCT01738828) of 7,726 patients, which includes a very large and deep set of measurements. First, the dataset includes extensive phenotyping of Lp(a) and its circulating isoforms, lipids, and lipoproteins. Second, the dataset also includes whole genome sequence data, whole genome methylation, whole transcriptome sequencing, proteomics, metabolomics and lipidomics, data. Finally, all these blood-based measurements are coupled with comprehensive phenotyping of atherosclerosis using cardiovascular computed tomography.  

Preliminary insights from G3 suggests that Lp(a) is not merely a biomarker; rather, Lp(a)-driven CVD is a distinct, high-risk cardiovascular phenotype, associated with higher atherosclerotic plaque burden, higher risk plaque, and higher prevalence of myocardial infarction.

Insights from this comprehensive analysis are expected to have significant clinical implications and will provide scientific basis for identifying the differential role of Lp(a) vs. other lipids and lipoproteins, such as Apolipoprotein B100 (apoB) and LDL-cholesterol, in the development of CVD. Anticipated results from the study will shed light on at least two critical clinical questions: (1) who are the highest risk patients with elevated Lp(a) who will benefit the most from potential future Lp(a)-lowering therapies, and (2) what is the role of elevated Lp(a) in patients with LDL-cholesterol levels already in the optimal range? In addition to atherosclerotic CVD, the project is also investigating the role of Lp(a) in the development of myocardial infarction, as well as in calcific aortic valve stenosis (CAVS).

"I have long known of and very much appreciated both the work and immense database developed by the research of the G3 consortium. As a well-recognized clinical and educational lipidologist, I understand the unlimited potential of leveraging their database to better understand and treat complex lipid and lipid/lipoprotein-related disorders. I had the opportunity to work with the G3 team on their novel discoveries related to TG-rich lipoproteins and I eagerly look forward to solving the mysteries / complexities of Lp(a) that I know G3 will uncover.", says Dr. Thomas Dayspring, MD, FACO, FNLA, Lipid Specialist at Early Medical.

The scientific initiative is supported by Novartis, and results are anticipated as early as mid-2024 from the initial analyses.

About the G³LOBAL Database™

G3 Therapeutic's G³LOBAL Database™ is derived from the GLOBAL clinical study (NCT01738828), an international prospective, multi-center study recruiting up to 10,000 patients to characterize novel disease networks and biomarkers. GLOBAL is the largest and most comprehensive pan-omic study combining whole genome sequencing, whole genome methylation, whole transcriptome sequencing, unbiased proteomics, metabolomics, lipidomics, and lipoprotein proteomics with coronary computed tomographic (CT) angiography, an advanced imaging technology for phenotyping, which allows the precise classification of disease in patients.

About G3 Therapeutics

G3 Therapeutics is a global leader in the application of unbiased biological big data in transforming the drug discovery and drug development process. G3 Therapeutics has assembled a revelatory platform that utilizes deep phenotyping, deep molecular profiling and deep learning for the discovery, genetic validation, and development of novel drug targets. G3 Therapeutics' foundational biological big data platform has been built on the GLOBAL Clinical Study (NCT01738828), enrolling over 7,500 individuals from around the world. G3 Therapeutics' deep molecular profiling approach includes whole genome sequencing, as well as the measurement of all other relevant "omics" measurements including DNA methylation, RNA sequencing, proteomics, metabolomics, and lipidomics. G3 Therapeutics has already discovered and patented relevant biomarkers and is starting the development of several novel drugs based on its proprietary platform and discoveries.

For additional information, please visit www.g3therapeutics.com 

SOURCE G3 Therapeutics