Science Review: PCSK9 assists LDL cholesterol determined cardiac health

Background: PCSK9 circulates in the blood, binding to the LDL receptor on the surface of liver cells, taking them into the cell to be degraded. On the surface, LDL receptors capture LDL cholesterol to remove it from the bloodstream. Mutating/inhibiting PCSK9 leaves more LDL receptors on the surface, thus reducing LDL cholesterol. Mutations in African Americans reduce heart disease by 90%.

Translational research: October 2012 phase II show fortnightly anti-PCSK9 mAb injections versus high statin treatment to reduce LDL cholesterol by 73% versus 17%. Two companies’ mAb-based phase III starting in 2013. Recourse to mAb has been necessary (but expensive) due to difficulty in making a suitable small molecule inhibitor.

Side point: Families with a mutation in PCSK9 that have high cardiac health implicitly have the mutation from birth, hence benefits of homologous drugs may be hidden if only given late in the game.