New study has revealed a novel family of blood thinners that work by blocking an enzyme found in the genes of tick saliva. Novel direct thrombin inhibitors from tick salivary transcriptomes, or messenger RNA molecules produced by an organism, were the focus of the study. As a consequence, new anticoagulant drugs are being developed to treat individuals suffering from a range of coronary problems, including heart attacks.
A new study out of the University of Cincinnati has uncovered a new family of blood thinners that work by blocking an enzyme found in the genes of tick saliva.
Novel direct thrombin inhibitors (DTI) from tick salivary transcriptomes, or messenger RNA molecules produced by an organism, were the focus of the study. As a consequence, new anticoagulant drugs are being developed to treat individuals suffering from a range of coronary problems, including heart attacks. The findings were reported in the journal Nature Communications.
“Evolutionary biology is firmly rooted in interest in ticks as a model for developing drugs that prevent blood clotting — [often] the cause of heart attacks and strokes,” says Richard Becker, MD, professor and director of the UC Heart, Lung, and Vascular Institute and the UC Division of Cardiovascular Health and Disease at the UC College of Medicine.
“Different blood clot inhibitory capabilities developed via a sequence of gene duplication events, according to a new evolutionary route revealed by backbone structure analysis. The evolutionary divergence of naturally occurring blood clot inhibitors in different tick species is estimated to have occurred about 100 million years ago.”
Becker was a co-author on the work, which found DTIs from tick salivary transcriptomes and maximized their application as a medicine. The most powerful is a major regulatory enzyme in blood clot formation with very high specificity and binding capacity, over 500 times that of bivalirudin, a medication used in a common nonsurgical technique to treat coronary artery constriction. In the United States, around 1 million people get these minimally invasive treatments each year.
“Despite their better capacity to prevent the production of blood clots, the medications showed less bleeding in nonhuman animals, establishing a broader therapeutic index,” Becker adds. “Because the medicine is more potent, it isn’t essential to use as much of it to treat patients, lowering the cost of products and production.”
Tick saliva, like that of other blood-feeding insects such as mosquitos, sand flies, tsetse flies, and black flies, includes pharmacological and immunological active chemicals that modify immune responses and promote antibody formation, according to Becker. Understanding of tick-host interactions and antibody production was used in this study.
“Specificity, selectivity, effectiveness, and safety have long been the holy grail of anticoagulant treatment,” adds Becker. “Clinician-scientists must be trained and work in an atmosphere that encourages them to ask questions and seek answers, especially those hidden in nature. For safety reasons, the capacity to assess and alter the medication dosage as well as quickly reverse its effects is critical. Before starting clinical trials in people, the next phase is to complete pharmacology, toxicology, drug stability, and other necessary regulatory requirements.”
