A recent news story
covered the development of drugs targeting PCSK9, a “pro-protein” that decreases the density of LDL receptors (e.g. in the liver). The interesting part for the computational biologist is the regulation of LDL receptors: The density of LDL receptors depends on the amount of LDL available in the bloodstream. With more LDL, their density increases. Another way to increase LDLR density are statins (drugs). However, statins also activate PCSK9. And PCSK9 acts to decrease LDL. In other words, it looks as if we have a classic homeostatic regulation, and by interfering with it at one point, we may activate processes that counteract the wanted drug effect. If we add PCSK9 inhibitors now (by monoclonal antibodies, or as in this case by miRNA interference), we believe we may have a more radical effect on keeping LDLR active. In any case, it tells us that we need to understand a system that we interfere with.
computational biology blog 