CytoVas aims to improve the assessment of cardiovascular health. The early-stage, in vitro diagnostic company is working to improve its Vascular Health Profile (VHP). Based on cytomics, which analyzes cell systems and networks, VHP is a blood test that gives a comprehensive view of a person’s cardiovascular health status. The firm says VHP also can be used by pharmaceutical companies to develop safer drugs.
VHP consists of a panel of biomarkers that reflect damage and repair to the cardiovascular system. The biomarkers measured are related to microparticles and endothelial progenitor cells. Microparticles reflect cell death or damage to the vasculature, whereas endothelial progenitor cells reflect blood vessel repair capacity. Currently, 13 biomarkers are measured, and the VHP panel can be customized to optimally address specific applications. “That’s part of our strategy to appeal to different markets,” says Pascal Yvon, Pharm.D., former CEO.
The technology behind VHP was a spin-off of discoveries made by researchers at the University of Pennysylvania. It combines cytomics, single-cell analysis, and data mining. Three Penn researchers—Emile Mohler, M.D., Jonni Moore, Ph.D., and Wade Rogers, Ph.D.—and Penn’s Upstart Incubator co-founded CytoVas in 2010.
The biology of cardiovascular disease, and many other illnesses, is extremely complex. Cytomics offers a method to look at both the genetic and environmental influences of a disease. Compared to genomics, which focuses on genes, and proteomics, which covers proteins, cytomics captures the molecular integration of genes and proteins, as well as modulating environmental factors like smoking and diet. “The beauty of cytomics is that it shows single-cell phenotypes of individuals resulting from genes and environmental exposures,” says Dr. Yvon.
Cytomics takes a top-down approach to looking at a disease. “We start with phenotypes and link them to what we observe about a disease,” says Dr. Yvon. This is easier than genomics and proteomics, he says, which are bottom-up approaches. A top-down approach looks at the single-cell level of an individual, while genomics and proteomics look at biomolecular events in cell populations.
Recent and dramatic improvements in instruments, markers, reagents, and data analysis make cytomics a valuable tool for studying diseases. “Cytomics offers an efficient alternative to systemically explore the biocomplexity of human organisms and is more closely related to explaining a disease state,” says Dr. Yvon.
The technology platform at CytoVas analyzes millions of cells at a rate of 100,000 events/second, and the high-throughput and high-dimensional analysis is very sensitive and specific, says Dr. Yvon. It relies on flow cytometry and cytometric fingerprinting, which interprets the huge volume of data generated. Cytometric fingerprinting identifies patterns or signatures that are relevant for a clinical diagnosis in an unbiased way.
In general, microparticles are involved in vascular damage caused by smoking, high cholesterol levels, high blood pressure, diabetes, and other stressors. High levels of microparticles occur in clinical conditions where vascular dysfunction and inflammation are important pathophysiological mechanisms, such as coronary artery disease.
On the other hand, maintenance of healthy blood vessels and repair of vascular damage involves endothelial progenitor cells, which originate in bone marrow. When endothelial damage occurs, cellular signals direct endothelial progenitor cells to the site of damage for repair. “In a healthy person, damage and repair mechanisms are in balance. But in an unhealthy person, damage overwhelms repair,” says Dr. Yvon.
Proof-of-concept studies at CytoVas show that high levels of microparticles and endothelial progenitor cells differ significantly between patients with type 2 diabetes (a model for vascular damage) and healthy controls. The ideal situation is low microparticles and high endothelial progenitor cells. “VHP visualizes the state of cardiovascular health, and no two people are the same,” says Dr. Yvon.
CytoVas sees several likely applications for VHP. Pharmaceutical and other companies developing drugs may benefit by selecting efficacious compounds and ruling out drug candidates that negatively impact the cardiovascular system. VHP can lower drug development costs and streamline the process of detecting damage early in the drug development pipeline. Additionally, companies designing clinical trials can use VHP to optimize the selection of patients.
“You want to identify and include patients who will respond best to a new drug,” says Dr. Yvon. Companies also can use VHP as a companion diagnostic to their cardiovascular drugs.
Another market is as a diagnostic test for physicians to help individualize the treatment of patients. “Physicians can use the information from the VHP to decide a course of treatment for a patient,” says Dr. Yvon. Then VHP can monitor a patient’s response to a treatment plan. Current tests, such as cholesterol levels, do not give an accurate picture of cardiovascular health, says Dr. Yvon, who notes that 50–75% of people who experience heart attacks have normal cholesterol levels.