The functionality of many drug candidates can be extremely difficult to study, particularly when dynamic processes on a scale larger than a drug’s molecule, such as blood flow, are involved. A research team has just used a “blood-vessel-on-a-chip,” a device developed at Harvard’s Wyss Institute, to identify a set of synthetic molecules that has impressive abilities to prevent clot formation while keeping the levels of thrombin, the body’s most important coagulant, at safe levels. The discovery is described in the latest issue of the Proceedings of the National Academy of Sciences.
The new compounds are based on, activated protein C (APC), an anti-coagulant naturally produced by the body that is also an anti-inflammatory compound. While APC does a good job, too much of it prevents the functionality of thrombin and therefore increases the potential for bleeding. The researchers identified so called parmodulins as having positive antiinflammatory and antithrombotic abilities thanks to their promotion of cytoprotective chemical signals and blockage of destructive signals.
“We essentially performed a mini pre-clinical trial of parmodulins’ effect on the endothelium, and not only determined the pathway through which parmodulins function, but also demonstrated that they help protect endothelial cells from inflammatory damage,” said a researcher on the study, former Wyss postdoc Abhishek Jain, Ph.D., now at Texas A&M University.