New medicines for treating heart patients: Genetic sequencing from ticks key in drug development

The University of Cincinnati discovered a class of medications that act as blood thinners by blocking an enzyme in the genes of tick saliva.

The research focused on novel direct thrombin inhibitors from tick salivary transcriptomes. The result is the development of new drugs that can be used to treat patients with a variety of issues, including heart attacks. Nature Communications published the study.

Richard Becker, MD, professor and director of the UC Heart, Lung and Vascular Institute and UC Division, says that interest in ticks as a model for developing drugs that prevent blood clotting is firmly based on evolutionary biology.

The analysis of backbone structures suggests a novel evolutionary pathway by which different blood clot inhibiting properties evolved. An evolutionary divergence is thought to have taken place 100 million years ago.

Researchers from the National University of Singapore, Duke University and the University of North Carolina collaborated with Becker on the study, which discovered dopaminergic substances from tick salivary transcriptomes. Bivalirudin, a drug used during a typical non surgical procedure used to treat narrowing of the coronary arteries, is almost 500 times more potent than the key regulating enzyme in blood clot formation. In the United States, about 1 million minimally-invasive procedures are performed each year.

The drugs achieved a wider therapeutic index in nonhuman models despite their greater ability to reduce the incidence of blood clot formation.

Becker says that tick saliva is similar to others that feed on blood like mosquitoes, sand flies, tsetse and black flies. Understanding tick-host interactions and the formation of antibodies was the focus of this research.

The holy grail of anticoagulant therapy has always been specificity, efficacy and safety. The ability to quickly reverse the effects of a drug is important for safety. The next step is to complete important regulatory steps before conducting clinical trials in humans.

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The University of Cincinnati provided the materials. Bill wrote the original. Content can be edited for style and length.

Journal reference

1. Cho Yeow Koh, Norrapat Shih, Christina Y. C. Yip, Aaron Wei Liang Li, Weiming Chen, Fathiah S. Amran, Esther Jia En Leong, Janaki Krishnamoorthy Iyer, Grace Croft, Muhammad Ibrahim Bin Mazlan, Yen-Lin Chee, Eng-Soo Yap, Dougald M. Monroe, Maureane Hoffman, Richard C. Becker, Dominique P. V. de Kleijn, Vaishali Verma, Amita Gupta, Vijay K. Chaudhary, A. Mark Richards, R. Manjunatha Kini, Mark Y. Chan. Efficacy and safety of next-generation tick transcriptome-derived direct thrombin inhibitors. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-27275-8