Researchers at the Vrije Universiteit Brussel have taken a significant step forward in the development of a new generation of gene therapy for haemophilia B, an inherited blood-clotting disorder. Their findings, published in the leading journal *Blood Advances*, show that a modified form of the therapy works significantly better in animal models than the current approach, without any additional safety concerns.

Haemophilia B is an inherited condition in which the body does not produce enough clotting factor IX. As a result, bleeding is difficult to stop and patients often require lifelong preventive treatment. Gene therapy offers the possibility of the body regaining the ability to produce clotting factor IX for the long term after a single treatment, but current therapies do not yield the same results in every patient. Up to 13 per cent of patients ultimately have to switch back to regular treatments.

The research team led by Professors Thierry VandenDriessche and Marinee Chuah from the Faculty of Medicine and Pharmacy has therefore developed a new approach. They linked an extra-potent variant of clotting factor IX to a modified form of human albumin, a protein that occurs naturally in abundance in the blood. As a result, the clotting factor remains in the bloodstream for longer and can perform its function more efficiently.

In mouse models, this new gene therapy yielded remarkable results. The animals produced around four times more clotting factor IX and exhibited three times more clotting activity than with the current approach. Their tendency to bleed was corrected for the long term.

Equally important is the fact that the researchers found no evidence of any additional safety risks. No harmful immune reactions or liver damage occurred, nor did the risk of unwanted blood clots increase. Furthermore, in most of the treated animals, the immune system developed tolerance to the new clotting factor, reducing the likelihood that the body will reject the therapy.

“Gene therapy has the potential to fundamentally change the lives of people with haemophilia, but at present the treatment does not yet work optimally for everyone. With this new approach, we demonstrate that we can significantly increase efficacy without compromising safety. This opens up prospects for a next generation of gene therapies,” says Prof.Thierry VandenDriessche.
“By combining a more potent and longer-acting clotting factor with gene therapy, we may be able to use lower doses of the viral vector. This would not only improve efficacy but also reduce the risk of immune reactions,” adds Prof. Marinee Chuah.

Although the results are currently limited to preclinical research, the researchers see significant potential for future clinical trials. If the findings are confirmed in humans, this approach could lead to more effective, sustainable and safer treatments for patients with haemophilia B. The research was made possible thanks to Methusalem Excellence funding from the Flemish Government and the Industrial Research Fund (IOF).

Contact:

Prof. Thierry VandenDriessche
Thierry.vandendriessche@vub.be
0477529653