Versiti Blood Research Institute Articles
Using Cutting-Edge RNA Therapies to Treat Bleeding and Clotting
Versiti Blood Research Institute’s Christian Kastrup, PhD, and his lab are developing new genetic therapies for treatment of bleeding disorders and blood clots.
According to the National Hemophilia Foundation, approximately 3 million people nationwide are affected by bleeding disorders. For most of these patients, their blood contains enough of the coagulation proteins that make clots and stop bleeding. However, for these patients, blood clots degrade quickly, causing excessive bleeding. Versiti Blood Research Institute Senior Investigator Christian Kastrup, PhD, and his laboratory are working to develop RNA-based gene therapies for patients with bleeding disorders and blood clots.
Improving treatments for patients with bleeding disorders
Key to improving the lives of patients with bleeding disorders is decreasing the rate at which clots degrade. “There are a number of bleeding disorders, both rare and less rare, where the concentration of blood proteins is not ideal, and that’s what causes the bleeding disorder or thrombotic disorder,” Dr. Kastrup said. “We’re developing an RNA gene therapy that can remove a lot of that clot degradation. We’ve tested it in many models of bleeding disorders, and it works well for stabilizing blood clots and decreasing bleeding.”
Tranexamic acid, a small-molecule drug, is commonly used to treat minor bleeding and encourage clotting in patients with bleeding disorders like hemophilia and von Willebrand disease. It is often used in conjunction with other blood products and factor replacement therapy for a holistic approach; however, it is cleared from the bloodstream within two to three hours and is meant to be used prophylactically, not long term.
Dr. Kastrup and his lab are focused on creating a drug similar to tranexamic acid that could be used long term and by patients who may be ineligible for traditional treatment options. “Because some patients have a bleeding disorder that is only classified as minor or moderate, they’re not eligible for many types of treatment for hemophilia. Or, they may have a rare disorder that doesn’t have any type of factor therapy,” Dr. Kastrup said. “We’ve leveraged all of the scientific advances in RNA therapy over the last 10-20 years to make a long-acting drug that could potentially be used once a month for improving health equity for people—particularly women—with bleeding disorders.”
New treatments for thrombosis and hemorrhage control
In addition to researching better treatments for patients with bleeding disorders, Dr. Kastrup’s team is working on RNA-based gene therapies related to thrombosis, with a focus on fibrinogen. “Fibrinogen is a really important protein in blood clotting. In many situations, including sepsis, inflammatory diseases and cancer, the amount of fibrinogen in the blood drastically increases,” he said. An excessive amount of fibrinogen in the blood can cause harmful blood clots to develop, and Dr. Kastrup’s lab is researching ways to bring fibrinogen back to normal levels and decrease the risk of adverse clotting.
His lab is also studying ways to control hemorrhaging and how to improve the efficacy of blood products. Platelets are often used to control bleeding and promote clotting, but they’re only effective to a certain point. “Platelets are a key component of trauma care, but they have their limit,” Dr. Kastrup said. “Once a bleed is too large, normal, natural platelets are ineffective. There are times when it would be better to use smaller amounts of next-generation blood products.”
To create these next-gen blood products, Dr. Kastrup’s lab studies donated platelets that are unable to be used by patients and enhances them to make them more useful for hemorrhage control. “We take these RNA therapies, and we modify the platelet to express a new protein in order to make these platelets more effective for the worst types of bleeds,” he said. “We hope that this product, along with the others we are developing, will improve mortality and morbidity from hemorrhage, surgical bleeding, bleeding disorders and thrombosis.”
“Versiti Blood Research Institute is the top site for blood research in the world,” he added. “Our researchers are at the top of their fields, and our collaboration with the Medical College of Wisconsin makes VBRI the ideal place to take this research from the bench to the bedside.”
Christian Kastrup, PhD, is a senior investigator at Versiti Blood Research Institute. He is also a professor in the Department of Surgery, Division of Trauma and Acute Care Surgery, and the Departments of Biochemistry, Biomedical Engineering, and Pharmacology and Toxicology at the Medical College of Wisconsin.
- Juang LJ, Hur WS, Silva L, Strilchuk A, Francisco B, Leung J, Groeneveld D, La Prairie B, Chun E, Cap A, Luyendyk J, Palumbo J, Cullis P, Bugge T, Flick M, Kastrup CJ, “Suppression of fibrin(ogen)-driven pathologies through controlled knockdown by lipid nanoparticle delivery of siRNA”, Blood, 2022 139:1302-1311. doi: 10.1182/blood.2021014559. PMID:PMC8900269.