Willard Freeman, Ph.D., from the College of Medicine at Pennsylvania State University, who conducted an alcoholism study with Kent Vrana, also from Penn State, and Kathy Grant from the Oregon National Primate Research Center, will talk about primate-based research at the meeting. “Right now there is no definitive clinical test to determine whether someone has an ongoing alcohol abuse problem, but we are looking to change that,” Dr. Freeman says.
While there are social implications to these findings, Dr. Freeman emphasizes that it’s about making a definitive diagnosis. “Our goal is to create a tool to provide a starting point for treating problem drinking.”
In the study, plasma protein biomarker discovery and validation were undertaken using an alcohol self-administering non-human primate model system. The goal was to develop a diagnostic that accurately classifies subjects into nondrinking, non-abusive drinking, and abusive drinking categories.
Plasma protein profiling was performed at Rules-Based Medicine (RBM). Initial biomarker discovery was conducted by multiplex Luminex analysis of 90 known plasma cytokines, growth factors, and other proteins samples. As a result, a 17-plasma protein panel was determined that correctly classified abusive drinking with 100 percent sensitivity and also differentiated any level of drinking from alcohol abstinence with 88 percent accuracy,” Dr. Freeman says.
The results of this well-controlled monkey model should be validated in humans next, he adds. “The panel provided by RMB represents proteins from the entire body. Being able to stratify the monkeys into three groups is an important part of the study, since differentiating socially acceptable drinking from excessive is critical.”
Metabolites constitute a broad range of biochemicals, including clinically accepted biomarkers like glucose or cholesterol, and serve as the core of Metanomics Health’s mass spec profiling platform, which the company uses to analyze a endogeneous and xenobiotic metabolites from body fluids and tissues, such as amino acids, lipids, carbohydrates, and many more, notes Tim Boelke, Ph.D., managing director.
“The science has evolved to a point where many of these small potential biomarkers can be simultaneously measured and provide a snapshot of biochemical homeostasis and physiological status, or its response to disease or drug treatment.”
Kristina Busch, Ph.D., business development manager, says that the company’s mass spec-based platform combines a broad profiling approach with targeted methods to provide the greatest coverage of nearly all metabolite classes. “We can also find low-abundance hormones such as catecholamines and steroids, as well as different classes of lipids and highly polar species. We’re gearing toward prospective and retrospective biomarker studies in high medical need areas.”
Since metabolism is sensitive to changes induced by drugs and diseases and also confounding factors like nutrition, lifestyle, and environment, robust study design practices and sampling are important to a successful biomarker identification campaign.
“This is not unlike all biomarker discovery methodologies like transcriptomics and proteomics. But, because of the sensitivity inherent in measuring biological response to stimuli, our methods can be applied to all kinds of problems, from understanding the metabolic effects of different nutritional and exercise regimes to how you best feed a cell culture for a recombinant-protein bioreactor run,” explains Dr. Boelke.