<P> In the 1990s, researchers at the Cedars - Sinai Medical Center showed that injection of a synthetic version of the mutant ApoA - 1 into rabbits and mice could reverse vascular plaque buildup . </P> <P> Apo A-I Milano has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial . Recombinant adeno - associated virus 8 (AAV8) mediated Apo A-I Milano gene therapy in combination with low - cholesterol diet induces rapid and significant regression of atherosclerosis in mice . </P> <P> The first examination of using the mutant ApoA - 1 in humans was conducted through a three way collaboration between the University of Milan and the companies Pharmacia and Upjohn in 1996, focusing on treatment of atherosclerosis . </P> <P> The ApoA - 1 Milano Trial, published in JAMA in 2003, was the first published placebo controlled, 2 dose level, trial in humans . This was a secondary prevention trial in that those included were individuals who presented to a participating hospital with unstable angina and agreed to consent to a rigorous trial, well beyond usual clinical practice testing and treatment, testing whether this HDL protein variant, which was so effective in animals, would also work in humans . This trial was initiated by Steven Nissen of the Cleveland Clinic after prompting by Roger Newton of Esperion to examine the effects of the mutant protein using intravascular ultrasound imaging . Esperion provided the protein, code named ETC - 216, for the duration of the trial . </P>

What selection pressure could act on apolipoprotein a1-milano to help it spread through a population