KineMed's "High Resolution" In Vivo Pharmacology

Drugs often behave differently in intact animals (in vivo) from predictions behavior based on what they do in test tubes or culture dishes(in vitro). Furthermore, drugs often behave differently in humans than predictions based on what they do in intact animals. These differences in drug action are significant sources of failure, success being "lost in translation". Better ways to translate across these boundaries can have great impact on pharmaceutical R&D success.

KineMed has proprietary techniques for studying complex biological and biochemical processes in living organisms. KineMed informs drug discovery and development both pre-clinically and clinically. KineMed's platform provides deep insights that significantly improve our understanding of what constitutes health, of what deviations from healthy function characterize specific diseases, of what significant variations are there within a given disease, of what changes in function are induced by exposure to any given drug and whether or not these changes are likely to be beneficial.

The foundation of KineMed’s approach is the use of stable isotopes as constituents of biochemical “raw materials” such as water, cholesterol, glucose (i.e., blood sugar), etc. We often use “heavy” water, in which the hydrogens have been replaced with deuterium, an isotopic variant containing one extra neutron per hydrogen. Unlike radioactive isotopes, this compound is entirely safe and can be administered safely to both animals and man. When a living organism drinks heavy water, it mixes freely with all the rest of the water in the body (about 13 gallons in an 180 pound man). While the heavy water is present, any of the many biological molecules which use hydrogens from water as “ingredients” will also use the deuterium from heavy water. In this way, proteins, DNA, RNA, lipids, and other biomolecules become “labeled”; the faster they are being made, the more they become labeled with deuterium, We can easily obtain samples of accessible body tissues, body fluids such as blood plasma, cerebrospinal fluid, sputum, urine, etc. After isolating the biochemical we want to know about, we use a very sensitive form of mass spectrometry to determine the extent to which the material has deuterium in place of hydrogens. All material made before the exposure to heavy water will have hydrogen exclusively (the natural levels of deuterium are very low), while all the material made after drinking heavy water will have a mix of hydrogen and deuterium; the faster it has been made, the higher the proportion of deuterium in the sample. KineMed has spent the last decade conceiving of, creating, road testing, and validating its ways to measure crucial biochemical pathways and processes in animals and man.

KineMed’s approach, because it can distinguish newly made materials from pre-existing materials, allows changes to be seen in much shorter periods of observation than otherwise possible. This allows us to determine the rates at which slow processes are happening in weeks when other approaches take months or years. We can also “see” differences from one individual to another, and determine drug effects by measuring changes in each subject compared to their own situation before drug administration.

We can measure rates of cell division and cell death, for a variety of cell types or tissues, such as nerve cells in memory regions of the brain, cancer cells, or skin cells, for example. We can measure how fast cartilage or fibrous tissue are being formed or degraded. We can determine how much cholesterol is being “ferried” by HDL from sites of excess such as atherosclerotic plaques to sites where it is either needed or excreted. We can measure rates of fat deposition and determine how much glucose the tissues are burning to give rise to carbon dioxide and water. Most of these measurements have not been possible before KineMed’s innovations.

With this armamentarium, we are exceptionally positioned to ask and answer some of the looming questions encountered in pharmaceutical R&D: questions that point to success or failure depending on which way the answers break. We can shed light on these crucial questions much more quickly and cheaply than otherwise possible; we can generate timely information providing better insights at key decision points all along the pharma R&D “value chain”.