Haemophilia A is a genetic disease that affects blood coagulation, and is caused by mutations of the Factor (F) VIII gene. At the present moment in time, treatment consists of substitution therapy with recombinant or plasma-derived FVIII inhibitors, administered as prophylaxis or according to need. The two biggest limitations of this treatment are the high costs and development of antibodies which neutralise FVIII activity in around 30% of patients, who must then be treated with other coagulants (meaning even greater treatment costs).

Identification of the mechanisms responsible for activation of immune response, and strategies to prevent it, can aid in the development of new therapies. Liver sinusoidal endothelial cells (LSEC) represent an interesting focus for gene therapy of correct FVIII expression thanks to their immuno-modulatory function and capacity for producing FVIII.

The research study, which will take place at the DISS Department of Università del Piemonte Orientale, pursues two main objectives:

1. The phenotypic definition of the immune cell populations resident in the hematolymphoid organs of mice affected by Haemophilia A
2. A study of the ability of LSEC cells to induce tolerance of FVIII in haemophiliac mice following gene therapy, in order to guarante stable production of an adequate amount of FVIII for the treatment of haemophiliac patients.