ApoA-1 Milano

Apolipoprotein A-1 Milano (also ETC-216, now MDCO-216) is a naturally occurring mutated variant of the apolipoprotein A1 protein found in human HDL, the lipoprotein particle that carries cholesterol from tissues to the liver and is associated with protection against cardiovascular disease. ApoA1 Milano was first identified by Dr. Cesare Sirtori in Milan, who also demonstrated that its presence significantly reduced cardiovascular disease, even though it caused a reduction in HDL levels and an increase in triglyceride levels.

Discovery

The ApoA-1 Milano mutation was found by University of Milan researchers after their 1974 investigation of a low HDL / high triglyceride phenotype exhibited by Valerio Dagnoli of Limone sul Garda, a small village in northern Italy. Limone had only 1,000 inhabitants at the time and when blood tests were run on the entire population of the village, the mutation was found to be present in about 3.5% of the local population. The mutation was traced to one man, Giovanni Pomarelli, who lived in the village in the late 18th century and passed it on to his offspring. It is characterised by the replacement of arginine by cysteine at position 173.