AT04A, a peptide-based formulation that induces an immune response against a protein that interferes with cholesterol clearance, has been effective in lowering cholesterol in studies with mice. AT04A qualifies as an immunotherapy, as it targets one of the body’s own proteins–not a protein associated with a pathogen.
The study is the first to demonstrate that the AT04A vaccine induced high and persistent’ antibody levels against PCSK9 (an enzyme that prevents the clearance of low-density lipoprotein cholesterol–‘bad’ cholesterol–from the blood).
When the AT04A formulation was injected under the skin of mice that had been fed diets of fatty 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%, in comparison to the unvaccinated mice. Moreover, the induced antibodies remained functional over the entire study period, and concentrations were still high at the study’s conclusion.
“The way that AT04A is administered is comparable to a vaccine,” explained Gunther Staffler, PhD, the chief technology officer at the company that initially developed AT04A. “However, the difference between a conventional vaccine and our approach is that a vaccine induces antibodies that are specific to bacterial or viral proteins that are foreign to the body—pathogens—whereas AT04A induces antibodies against a target protein that is produced by the body—endogenous proteins. This it is really an immunotherapeutic approach rather than a vaccine approach.”