The First Vaccine to Lower Cholesterol

저자：   업로드：2017-06-22  조회수：

    It gives rise to antibodies that could prevent disease, but it’s not quite a vaccine. It qualifies as an immunotherapy because it targets one of the body’s own proteins, not a protein associated with a pathogen. The “it” in this case is AT04A, a peptide-based formulation that induces an immune response against a protein that interferes with cholesterol clearance.

    According to a recent study, AT04A lowered cholesterol in a mouse model of atherosclerosis. This result, detailed June 19 in the European Heart Journal, is an encouraging sign that AT04A may also perform well in humans. A Phase I study is, in fact, currently under way. If this study establishes that AT04A is both active and safe, it will encourage further evaluations, which may culminate in the development of effective treatments to prevent cardiovascular disease.

    The mouse study (“The AT04A Vaccine against Proprotein Convertase Subtilisin/Kexin Type 9 Reduces Total Cholesterol, Vascular Inflammation, and Atherosclerosis in APOE*3Leiden.CETP Mice”) is the first to show that it is possible to immunize genetically modified mice with a molecule that causes the body to produce antibodies against an enzyme called PCSK9 (proprotein covertase subtilisin/kexin type 9), which plays a role in preventing the clearance of low-density lipoprotein cholesterol ("bad" cholesterol) from the blood.

    The AT04A vaccine induced high and persistent antibody levels against PCSK9, causing a significant reduction in plasma total cholesterol and bad cholesterol compared with controls.

    “Plasma inflammatory markers such as serum amyloid A (SAA), macrophage inflammatory protein-1β (MIP-1β/CCL4), macrophage-derived chemokine (MDC/CCL22), cytokine stem cell factor (SCF), and vascular endothelial growth factor A (VEGF-A) were significantly diminished in AT04A-treated mice,” reported the authors of the European Heart Journal article. “As a consequence, treatment with the AT04A vaccine resulted in a decrease in atherosclerotic lesion area...and aortic inflammation as well as in more lesion-free aortic segments.”

    When the AT04A formulation was injected under the skin in mice that have been fed fatty, Western-style food, it reduced the total amount of cholesterol by 53%, shrank atherosclerotic damage to blood vessels by 64%, and reduced biological markers of blood vessel inflammation by 21% to 28%, compared to unvaccinated mice. Furthermore, the induced antibodies remained functional over the whole study period, and concentrations were still high at the end of the study.