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VBRI Senior Investigator Christian Kastrup Publishes Significant Study on Blood-Clot Prevention in Older Adults

Milwaukee — March 20, 2026
Blood clots can have deadly consequences, including heart attacks, strokes, and pulmonary embolisms. And older adults are at a disproportionately higher risk. A new study, published in the journal Blood, and led by Versiti Blood Research Institute (VBRI) Senior Investigator Christian Kastrup, PhD, suggests a new way to reduce that risk using precision gene targeting and potentially prolong lifespan.

Blood clots can have deadly consequences, including heart attacks, strokes, and pulmonary embolisms. And older adults are at a disproportionately higher risk. A new study, published in the journal Blood, and led by Versiti Blood Research Institute (VBRI) Senior Investigator Christian Kastrup, PhD, suggests a new way to reduce that risk using precision gene targeting and potentially prolong lifespan.

The culprit at the center of the research is a protein called PAI-1. In healthy amounts, this protein plays an important role in helping hold clots together long enough to heal wounds. As people age, however, PAI-1 levels in their blood increase and hinder the body’s ability to naturally break down clots. The result is a higher risk of dangerous clots forming in the body, cutting off circulation to the heart, lungs, or brain. Elevated levels of PAI-1 are also linked to obesity, diabetes, cancer, and neurodegenerative diseases. 

The Kastrup Lab’s approach targets the problem at its source. Researchers developed an experimental therapy using small RNA molecules (called siRNA) that essentially turn down production of the gene responsible for producing PAI-1. To deliver the therapy, they packaged these siRNA molecules inside lipid nanoparticles, microscopic fat-based capsules that can carry the therapeutics directly into patient cells.

In testing, the therapy dramatically reduced PAI-1 levels, offering a promising new strategy for preventing clots without the bleeding risks that come with conventional blood thinners. It also dramatically prolonged lifespan in fast-aging mice models without thrombosis.  

Once delivered into the body, the siRNA specifically targets the genetic instructions that cells use to produce PAI-1. By degrading the messenger RNA for this protein, the therapy prevents cells from making excess PAI-1. Remarkably, a single dose of siRNA reduced PAI-1 by about 90% for up to 10 days without noticeable side effects.

Once delivered into the body, the siRNA specifically targets the genetic instructions that cells use to produce PAI-1. By degrading the messenger RNA for this protein, the therapy prevents cells from making excess PAI-1. Remarkably, a single dose of siRNA reduced PAI-1 by about 90% for up to 10 days without noticeable side effects.

RNA-based therapies are an increasingly important area of medicine. Lipid nanoparticle delivery systems have already been used successfully in several approved treatments and vaccines, demonstrating their ability to safely deliver genetic material into the body.

According to the study, this technology could enable treatments that regulate proteins previously considered difficult to target with conventional drugs such as antibodies or small molecules. Because PAI-1 is implicated in a wide range of conditions, including cardiovascular disease, metabolic disorders, and neurodegeneration, reducing its levels could have outstanding benefits and for patients, the possibilities could truly be lifesaving.

“Current treatments often require long-term blood thinners that can increase the risk of bleeding,” says Kastrup. “A therapy that lowers PAI-1 with a single dose lasting 10 days could offer a more targeted and long-term alternative with fewer side effects.” Kastrup and his team imagine a future where older patients live longer, healthier lives while reducing complications from clot-related conditions such as heart attacks, strokes, and deep vein thrombosis.

The work also highlights the translational focus of research at Versiti Blood Research Institute, where scientists are combining expertise in blood biology with emerging technologies to develop new therapeutic approaches.

“This type of cutting-edge, translational research is exactly why VBRI is a leader in developing new strategies to prevent and treat blood-released diseases,” says Kastrup.

The team behind this study include: Francesca Ferraresso, PhD, Chad Skaer, Zimu Wei, Manoj Paul, PhD, Woosuk Steve Hur, PhD, Hongyin Yu, Monica Seadler, MD, Taylor Chen, Wen Dai, Catherine Lapointe, Laura Ketelboeter, PhD, Hayley Lund, Geoffrey Rodriguez, MD, Lih Jiin Juang, PhD, Amy Strilchuk, PhD, Youjie Zhang, Pieter Cullis, PhD, Mitchell Dyer, PhD, Allison Gerras, MS, DVM, DACVP, Qizhen Shi, MD, PhD, James Luyendyk, PhD, Matthew Flick, PhD, and Christian Kastrup, PhD.

 

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VBRI Senior Investigator Christian Kastrup Publishes Significant Study on Blood-Clot Prevention in Older Adults

A new study led by VBRI Senior Investigator Christian Kastrup, PhD, shows that a single dose of RNA-based therapy can slash levels of a clot-promoting protein by 90%, offering a promising alternative to conventional blood thinners for older adults.
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