When you suffer an injury or have a rupture in a blood vessel, the body typically initiates a process to stop the bleeding. Blood thickens, allowing you to stop bleeding. This process is known as blood coagulation.
However, individuals with bleeding disorders lack the ability for effective coagulation.
As a result, they can experience severe bleeding episodes, which in the worst cases can be life-threatening.
“Over 100 years ago, the life expectancy for a child with a bleeding disorder was around ten years. By the 1960s, this figure had increased to approximately 40 to 50 years, and today, the life expectancy is roughly equivalent to that of the rest of the population, thanks to medical treatment,” explains professor Jan Terje Andersen.
Treatment can be burdensome for children and their families
Bleeding disorders are caused by a hereditary genetic defect and last a lifetime. Primarily boys are affected, while girls can carry the gene defect without having the condition itself. Approximately 1 in 10,000 boys has the severe variant of the disease.
The disorder is often diagnosed in infancy. Children must quickly start preventive treatment to avoid further bleeding episodes. This treatment is administered intravenously, which means directly into a blood vessel.
Both children and adults may require treatment from once to several times a week.
“In the early years, most children must go to the hospital for treatment each time. From around the age of five, children can often be treated at home with their parents’ assistance. Eventually, as boys grow older, they can usually manage their treatment themselves,” explains Andersen.
“Particularly in the early years, the treatment can be a significant burden for both the child and the family,” he points out.
A new invention could make treatment for people with bleeding disorders less burdensome
Now, researchers at the University of Oslo and Oslo University Hospital in collaboration with international researchers have made an invention that could eventually ease the lives of people with bleeding disorders.
“We have designed a modified version of a natural protein that means individuals with bleeding disorders likely will not need to receive treatment as frequently as they do today. The modified protein is intended to extend the medication's duration of action, so it does not need to be administered multiple times a week or every week,” says Andersen.
The professor and his colleagues hope that their research can simplify life for boys and men with bleeding disorders.
The study has been published in Nature Communications?and featured?in a press release via EurekAlert!.
Why doesn’t blood coagulate in individuals with bleeding disorders?
Another term for coagulation—that is, the thickening of blood where an injury occurs—is clotting.
“In the severe variants of the disorder, the body lacks the ability to produce a type of protein crucial for blood-thickening. These proteins are known as coagulation factors,” explains the professor.
Currently, those with bleeding disorders are given a medication containing one of these coagulation factors that their bodies cannot produce independently.
“These factors are produced using biotechnological methods and have revolutionised treatment,” says Andersen.
“However, a significant challenge is that such recombinant coagulation factors have a limited duration of action in the bloodstream. This is why patients must receive the medication regularly, which could be up to several times a week,” he explains.
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The aim is to extend the duration of action of medications in the blood
In recent years, new knowledge combined with technology have led to the design of proteins that break down more slowly in the body. Medications for bleeding disorders are a prime example of such advancements.
“When the duration of action is prolonged, medications can be administered less frequently. The levels of coagulation factors remain higher in the bloodstream over time, even with smaller doses,” explains Andersen.
Thus, development is already heading in the right direction.
“Nevertheless, there are still considerable variations in the duration of action among the different medications that individuals with bleeding disorders rely on,” notes the professor, continuing:
“Therefore, there is significant potential to develop even better medications for bleeding disorders, which can enhance patients' quality of life.”
Designed proteins function as a kind of taxi for the medication
Andersen and his colleagues have further researched how such medications can be improved. The molecule they have designed is a variant of a protein called albumin.
“The modified protein is entirely unique and functions as a sort of taxi for the medication,” says the professor.
In the published study, the researchers demonstrate that by linking the new variant of albumin to a coagulation factor, it circulates in the bloodstream for an extended time.
“By utilising this technology, more of the medication will be available in the body over time. Therefore, we expect that the patient will not need to take the medication as often as they do today,” explains Andersen.
Testing the new concept on a mouse model for bleeding disorders
The researchers have tested the new concept in a mouse model for bleeding disorders. They compared various designs of the protein and observed a significant difference in the duration of action in the blood.
Furthermore, the researchers introduced a single modification in the coagulation factor itself to enhance blood coagulation efficiency.
To add further complexity, the researchers show that it is also possible to alter the distribution of the coagulation factor between the blood and tissue by making additional minor modifications.
“This can be leveraged in treatment to tailor the therapy to each individual patient,” says the professor, continuing:
“We therefore have great confidence that the tailor-designed proteins can make a significant difference in both preventive and acute treatment of bleeding disorders.”
Andersen intends to advance the concept for testing in humans
The professor of biomedical innovation has great faith in the potential of the new protein designs. Together with colleagues, he is now seeking collaborators from the pharmaceutical industry with expertise in bleeding disorders.
“In the new study, we describe entirely new strategies for how we can use molecular design to create long-acting coagulation factors with substantial clinical potential,” he states, adding:
“It would have been fantastic to translate the new concept into medications that can benefit patients with bleeding disorders.”
The project is based on extensive collaboration with international collaborators, including the laboratory led by Alessio Branchini and Mirko Pinotti at the University of Ferratra in Italy., and the research was financed through the Research Council of Norway, the South-Eastern Norway Regional Health Authority, the Novo Nordisk Haemostasis Grants Initiative and by the Fondo di Ateneo per la Ricerca from the University of Ferrara.
The research was funded by the Norwegian Research Council and Helse S?r-?st.
Andersen is head of one of the research groups in the Centre of Excellence PRIMA, funded by the Norwegian Research Council.?
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Reference
Aaen, K. H., Testa, M. F., Nilsen, J., Tarantino, R., Canepari, C., Benedusi, M., ... & Andersen, J. T. (2025). Tailored collagen binding of albumin-fused hyperactive coagulation factor IX dictates in vivo distribution and functional properties. Nature Communications, 16(1), 8433. The article can be accessed here.
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