A team of researchers at the University of New Mexico (UNM) and the National Institutes of Health (NIH) have developed a vaccine to treat high cholesterol. The vaccine, which targets a molecule called PCSK9, a protein involved in cholesterol metabolism, is a cost-effective alternative to current expensive cholesterol drugs and could lead to a widely applicable vaccine-based approach for controlling high cholesterol and cardiovascular disease. The study demonstrated that the vaccine dramatically lowered cholesterol levels in animals. The study, “A Cholesterol-Lowering VLP Vaccine that Targets PCSK9,” was recently published in the journal Vaccine by Dr. Bryce Chackerian, Professor in the Department of Molecular Genetics & Microbiology at UNM, Erin Crossey, an MD/PhD student at UNM, and Drs. Alan Remaley, John Schiller, and Marcelo Amar at NIH.
Genetic mutations that increase PCSK9 activity are linked to increased levels of low-density lipoprotein cholesterol (LDL-C—the “bad” cholesterol), which in turn is associated with an increased risk of plaque build-up in the arteries leading to coronary heart disease (CHD) and stroke. More than 73 million adults in the United States (approximately 32 percent of the population) have elevated LDL-C levels, or high cholesterol. Although lifestyle changes and medication (such as statins) can lower LDL-C, more than 60 percent of at-risk patients on lipid lowering therapy still go on to have a cardiovascular event.
Statins have side effects, including increased concentrations of liver enzymes, muscle pain, cognitive loss, increased risk of diabetes, and adverse drug interactions. As an alternative to statins, drug companies have developed monoclonal antibody-based drugs that target PCSK9, such as Alirocumab and Evolocumab that were recently approved by the FDA to treat high cholesterol. While these drugs have been shown to dramatically reduce LDL-C levels (by up to 60 percent) and cardiovascular events, they are extremely expensive, costing over $10,000 per year. This will likely limit the use of this class of drugs for those patients who cannot be effectively managed with statins or some of the other currently used cholesterol-lowering drugs. Additionally, monoclonal antibody therapies must be administered repeatedly for therapeutic effect.
The vaccine uses a VLP (virus-like particle) technology developed by Dr. Chackerian and his UNM co-inventors as an immunogenic carrier of an antigenic PCSK9 peptide. VLP’s are viruses that have had their DNA removed so that they retain their external structure for antigen display but are unable to replicate; they can induce an immune response without causing infection. VLP based vaccines are effective and safe and can be developed rapidly at low cost. In the study, mice and macaques vaccinated with bacteriophage VLPs displaying PCSK9-derived peptides developed high titer IgG antibodies that bound to circulating PCSK9. Vaccination was associated with significant reductions in total cholesterol, free cholesterol, phospholipids, and triglycerides. “We believe that this vaccine could lead to a widely applicable approach for controlling hypercholesteremia and cardiovascular disease,” Dr. Chackerian said.
The patent pending vaccine is good news not only for patients but UNM’s technology-transfer organization, STC.UNM (STC) as well. “This technology is a strong candidate for successful commercialization and could be an entirely new and effective way of treating diseases that are a result of untreated high cholesterol,” added STC CEO Lisa Kuuttila.
The online version of the study can be found on the journal’s website at http://dx.doi.org/10.1016/j.vaccine.2015.09.044. (“A Cholesterol-Lowering VLP Vaccine that Targets PCSK9,” by Erin Crossey, Marcelo J. A. Amar, Maureen Sampson, Julianne Peabody, John T. Schiller, Bryce Chackerian, and Alan T. Remaley. The article is now in press in Vaccine, Volume 33, Issue 43, pp. 5747-5755 (26 October 2015) published by Elsevier. Copies of this paper are available to credentialed journalists upon request; please contact Elsevier’s Newsroom at newsroom@elsevier.com or +31 20 4853564.
About Vaccine
Vaccine is the pre-eminent journal for those interested in vaccines and vaccination. It is the official journal of The Edward Jenner Society, The International Society of Vaccines and The Japanese Society for Vaccinology and is published by Elsevier. (www.elsevier.com/locate/vaccine)
About the UNM Molecular Genetics & Microbiology Department
The Department of Molecular Genetics & Microbiology’s key missions are in the areas of research, teaching, and service, which are aligned with the mission and the core values of the UNM School of Medicine and Health Sciences Center. The department prides itself on outstanding research leading to discoveries in basic cellular processes, disease mechanisms, and novel approaches to therapy. We strive to maintain the highest quality and impact in scientific knowledge, education and public health. One mechanism to reach this goal is the development of teams of outstanding investigators that interact in specific areas of focus. (http://mgm.unm.edu)
About STC.UNM
As the technology-transfer and economic-development organization for the University of New Mexico (UNM), STC.UNM (STC) protects and commercializes technologies developed at UNM by filing patents and copyrights and transferring them to the marketplace. We connect the business community (companies, entrepreneurs and investors) to these UNM technologies for licensing opportunities and the creation of start-up companies. STC’s vision is to play a vital role in New Mexico’s economic development and to be a leader in technology commercialization. Under the leadership of CEO Lisa Kuuttila, STC is substantially growing its program using the Rainforest model to develop an innovation economy in New Mexico. In 2013, STC was tasked by UNM with implementing its economic-development initiatives. For additional information, contact Jovan Heusser, STC Senior Innovation Manager & Innovation Team Lead, at (505) 272-7908 or jheusser@stc.unm.edu. To learn more about us, visit our website at www.stc.unm.edu.