new direct thrombin inhibitors (DTI) derived from tick salivary transcriptomes or messenger RNA molecules produced by an organism. As a result, new anticoagulant drugs have been developed that can be used to treat people suffering from a range of coronary disorders, including heart attacks.
According to Richard Becker, MD, professor and director of the UC Heart, Lung and Vascular Institute and UC Division of Cardiovascular Health and Disease at the UC College of Medicine, “Interest in ticks as a model for developing drugs that prevent blood clotting — [often] the cause of heart attacks and strokes — is firmly rooted in evolutionary biology”. He added, “Analysis of backbone structures suggest a novel evolutionary pathway by which different blood clot inhibiting properties evolved through a series of gene duplication events. Comparison of naturally occurring blood clot inhibitors of differing tick species suggests an evolutionary divergence approximately 100 million years ago.”
Becker collaborated on the project with academics from the National University of Singapore, Duke University, and the University of North Carolina. The study identified DTIs from tick salivary transcriptomes and improved their usage as a pharmaceutical. The most potent is a crucial regulator of blood clot formation with a high degree of specificity and a binding capacity over 500 times that of bivalirudin, which is a medicine used in a standard non-surgical therapy for coronary artery constriction. Each year, around 1 million people in the United States get these minimally invasive treatments.
Becker said, “Despite their greater ability to reduce the incidence of the formation of blood clots, the drugs demonstrated less bleeding, achieving a wider therapeutic index in nonhuman models”. He added, “The higher potency of the drug means it’s not necessary to use a lot of it in treating patients, which holds the cost of goods and manufacturing down.”
According to Becker, tick saliva, like that of other blood-feeding insects such as mosquitoes, sand flies, tsetse, and black flies, includes pharmacological and immunological active chemicals that regulate immune responses and promote antibody generation. This study made use of existing knowledge on tick-host interactions and antibody development.
Becker spoke about anticoagulant therapy. He said, “The holy grail of anticoagulant therapy has always been specificity, selectivity, efficacy and safety. Clinician-scientists must have the training and an environment that embraces asking questions and finding solutions, including those potential found deep within nature. An ability to both measure and adjust the drug dose and rapidly reverse its effects is particularly important for safety purposes. The next step is to complete pharmacology, toxicology, drug stability and other important regulatory steps before conducting clinical trials in humans.”
