Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Small Antibody Fragment as Alternative Tools in Haemophilia Care

Project Coordinator



David Lillicrap Queen's University Kingston, Canada
Federico Mingozzi Université Paris 6 Pierre Marie Curie Paris, France
Dirk GRIMM Heidelberg University Hospital Heidelberg, Germany

The functional absence of coagulation factor VIII (FVIII) is associated with a severe bleeding disorder, known as haemophilia A, affecting 1-2 per 10,000 males. Clinical management mainly involves replacement therapy using purified FVIII concentrates. Due to a number of disadvantages of this approach (frequent intravenous infusions, development of inhibitory antibodies, high costs), there is a strong medical need for the development of novel therapeutic strategies. The aim of the present project is to develop low-cost protein therapy and an innovative AAV-based gene therapy approach for haemophilia A using single domain antibody fragments (nanobodies). Nanobodies have several advantages, including a low (if any) immunogenicity when applied to humans. Further, their small size (±17 kDa) facilitates their molecular engineering and the incorporation of their cDNA in viral particles. Nanobodies will be generated targeting anticoagulants Antithrombin or Protein S. The absence of these anticoagulants restores the defective thrombin generation capacity in haemophilic mice. Indeed, preliminary studies by Partner 1 revealed that nanobodies targeting Antithrombin fully restore thrombin generation in haemophilic plasma. In this research program, we will explore two different modes of nanobody delivery: protein administration or gene transfer. The first approach will focus on the development of subcutaneous delivery, leading to an improved treatment regimen. The second approach provides the potential of a long-term therapeutic solution to minimize bleeding in haemophilia.

E-Rare 2012 - Created by Toussaint Biger