ApoA-1 Milano: Hope for a Cure or Hype for Profit?

Coronary plaque regression in just weeks? The initial clinical trial indeed suggested that this was achievable. And it wasn’t just another glowing report on a cholesterol drug, but an entirely new class: a recombinant mimic of a naturally-occurring mutant HDL protein.

ApoA1 Milano: A History

For centuries, the tiny village of Limone sul Garda in northern Italy was reachable only by boat or through a narrow mountain pass. As a result, the several hundred inhabitants of this secluded hamlet rarely married people from outside their community. This created a population that was unusually inbred.

In 1932, the Gardesana roadway was constructed, providing access to the rest of the world. But it wasn’t until 1979 that an ex-Limonite railway employee living in nearby Milan was hospitalized. The doctors noted that the man had an exceptionally low HDL cholesterol of 12 mg—ordinarily a high-risk marker for heart disease—yet appeared to be free of any evidence of atherosclerosis.

The inquisitive Italian doctors, Guido Franceschini and Cesare Sirtori, tracked the family roots of this man to other inhabitants of Limone. Through detailed history-taking, blood testing, and historical sleuth work, the researchers tracked the origin of the gene responsible for the peculiar low HDL unassociated with heart disease back to a Limone couple that married in 1700. A fortuitous gene mutation or combination from inbreeding allowed the emergence of a gene that, despite low measured HDL, appeared to confer protection against atherosclerosis.

Thus was born the mis-named “ApoA-1 Milano” that has triggered a flurry of research. In 1998, a venture capitalist launched Esperion Therapeutics in Ann Arbor, Michigan, and hired Roger Newton as CEO, the man who had championed development of Lipitor.

The Cleveland Clinic Study

Administration of ApoA-1 to animals showed beneficial changes in plaque even after a single dose. Based on favorable experimental observations, in 2004 Dr. Steven Nissen of the Cleveland clinic published the results of a preliminary human study administering a recombinant form of ApoA-I Milano.

The preparation used, dubbed ETC-216, was a hybrid of the unique protein of the Italian HDL, ApoA-I, and a phospholipid carrier molecule. Forth-seven participants, all of whom had coronary disease and were enrolled within two weeks of an acute coronary event (unstable angina, heart attack) agreed to receive intravenous ETC-216 once a week (2 groups: low- and high-dose) vs. placebo infusion for a total of five doses. Intracoronary ultrasound (ICUS) was performed in a single site in one artery both before and following the completion of the course of infusions. (Intracoronary ultrasound is an invasive procedure performed during cardiac catheterization that provides detailed cross-sectional images of coronary plaque; its limitation is that it requires catheters to be passed directly down your coronary artery and thus carries risks. It is therefore not appropriate as a screening procedure in well people.)

Of the 47 people completing the study, 21 received low-dose ETC-216, 15 received high-dose, and 11 received placebo. Several people withdrew from the study for a variety of reasons; two withdrew due to possible reactions to ETC-216 involving chills, vomiting, and rash.

Comparing pre- and post-ICUS, participants receiving placebo had 2.9 mm3 (1.7%) reduction in plaque volume. Low-dose recipients showed a 15.1 mm3 (5.1%) reduction in volume, while high-dose recipients showed a 12.6 mm3 (5.4%) reduction.

This report understandably triggered great excitement. It appeared to confirm the long-held theory that HDL was indeed a facilitator of coronary plaque regression. The results were especially remarkable in that regression was observed with just a few doses and within a few weeks.

When the report of the trial first hit the media, we got daily questions about how people could get their hands on it. “Drano for arteries!” declared headlines.

Tremendously exciting, particularly for those of us interested in plaque regression. But what’s likely to be the reality? How do we see this agent fitting into a focused program of regression?

Any Value for Track Your Plaque Plaque Regression Program?

Want to read the rest of this Track Your Plaque Special Report? Already a member? CLICK HERE to log-in. Want to become a member? CLICK HERE Want to learn more about the benefits of membership? CLICK HERE

Copyright 2006, Track Your Plaque.