Atherosclerosis - ETC-216
Atherosclerosis is caused by the deposition of fatty substances in the medium and large arteries, which form a plaque that can block blood flow and may lead to stroke, coronary heart disease or myocardial infarction.
The major risk factor is a high serum level of cholesterol, and high circulating levels of low density lipoprotein (LDL), the main transporter of cholesterol around the body, are particularly dangerous. However, another cholesterol carrier, high density lipoprotein (HDL) has a protective effect. The first strategy to reduce LDL levels is by dietary changes, but if unsuccessful the next step is to use LDL reducing drugs such as the statins.
An alternative strategy would be to raise HDL levels, as if these get too low then they also present a risk of coronary disease. Combined with LDL reduction, this could present an attractive therapeutic option. HDL comprises cholesterol and phospholipids, and a range of apolipoproteins. One of these, apo-A-I, makes up around 70% of total HDL protein. A recombinant form has been produced in E. coli by Esperion Therapeutics, now part of Pfizer. When complexed with the naturally occurring phospholipid 1-palmitoyl-2-oleoylphosphatidylcholine, it makes a synthetic HDL, and this is being investigated as a potential atherosclerosis treatment.
A trial was carried out in healthy volunteers, and showed that it was well tolerated and also increased HDL levels.1 A multicentre randomised double blind placebo-controlled trial in 57 patients with acute coronary syndromes looked at the effects of weekly infusions of ETC-216.2 It was given in doses of 15 or 45mg/kg for five weeks. A significant reduction in atheroma volume was seen in the 47 patients who completed the trial, with a mean 4.2% reduction in those given active. In contrast, those given placebo saw the volume rise by a mean of 0.14%. Phase II trials continue.