The technology, which consists of a specially developed variant of a naturally occurring protein called super albumin, can pave the way for long-acting drug development. This can have serious consequences for people with haemophilia.
When an injury or a hole occurs in a blood vessel, the body quickly begins to stop the bleeding through a process called clotting, or clotting. The blood then thickens a little at the bleeding site. For most of us, this process goes smoothly. However, in patients with a severe bleeding disorder or haemophilia, the blood lacks the ability to clot.
Patients with a bleeding disorder or haemophilia have a genetic abnormality and the condition is hereditary and lifelong. Both girls and boys can carry the genetic abnormality, but only boys get the disease.
Hemophilia can have different degrees of severity, but the severe variant is the most common, with around one case in 10,000. It is caused by the body’s decreased ability or inability to produce one of several factors called clotting factors. These factors are important in the process of blood clotting, which stops the bleeding. Without treatment, the disease can be life threatening.
Preventive treatment is very important
More than 100 years ago, the life expectancy of a sick child was around ten years. However, in the 1960s, life expectancy rose to 40-50 years due to access to medical treatment. Life expectancy today is almost as high as that of other newborns.
This is because bespoke drugs have been developed using biotechnological methods. They are made from recombinant coagulation factors that are made in the laboratory and that can be given as a preventive treatment to prevent repeated bleeding.
Treatment puts a strain on children and their families
Hemophilia is often discovered around a year old, after which preventive treatment is started. This is important to avoid recurring bleeding as it leads to persistent stiffness and limited range of motion.
The medicine will be given intravenously directly into the vein up to several times a week. This is stressful for both the child and their families as they have to go to the hospital. However, children around the age of five can be treated at home with the help of parents and over time, patients can self-medicate.
A major challenge is that the coagulation factors in the bloodstream have a very short duration of action, which requires frequent administration of the drug. Nevertheless, medical progress has led to the otherwise short-acting drugs being redesigned so that they are broken down a little more slowly in the body.
Super-albumin technology can be used to develop long-acting drugs
A longer duration of action means that you can take the medicine less often and still have a steady coagulation factor over time. This makes a significant difference to the patient. However, there are still major differences depending on which coagulation factor the patient is missing. There is therefore still a lot of room for improvement.
Our research group has developed a unique biomedical technology with which coagulation factors can be produced with a significantly longer duration of action than today. The starting point is in-depth studies of a biological mechanism. This insight has enabled us to develop super-albumin, an evolved variant of protein that can be coupled to protein-based drugs and allow them to remain in the bloodstream for a considerably longer period of time.
We show that by combining super albumin with various coagulation factors, the duration of action can be significantly extended compared to the current treatment. This is achieved by combining a bespoke molecular design with a series of experiments carried out in the best experimental setups available. The results motivate further tests on humans.
Opens up to new possibilities
Superalbumin is a versatile technology that can be used to extend the duration of action of any protein-based drug candidate. That’s why we’re now working to test the technology in various medical fields, including cancer and infectious diseases. We do this in our own laboratory, but also together with biotech companies.
In addition, we have shown that super albumin can be transported across mucosal barriers. This opens up exciting new ways in which we can envision delivering albumin-based drugs through selective barriers to the nose, lungs, or intestines without the use of syringes. We are now examining this possibility.
The work is based on a very fruitful collaboration with a hematology research group working on blood diseases in Ferrara, Italy, led by Mirko Pinotti and Alessio Branchini.
Source:
University of Oslo, Faculty of Medicine
Journal references:
- Bern, M., et al. (2021) An engineered human albumin improves half-life and transmucosal release when it is fused with protein-based biologics. Science Translational Medicine. doi.org/10.1126/scitranslmed.abb0580.
- Lombardi, S., et al. (2021) The fusion of engineered albumin with Factor IX Padua extends the half-life and improves coagulation activity. British Journal of Hematology. doi.org/10.1111/bjh.17559.
