Project: Use of patient-specific induced pluripotent stem cells to improve diagnosis and treatment of Hemophilia A

The blood-clotting disorder Hemophilia A (HA) is a rare disease caused by mutations in the F8 gene, for which there is a clear need to develop novel disease models based on the relevant cell types that physiologically express F8. Patient-specific induced pluripotent stem cells (iPSC) offer unprecedented ways to model human diseases in a way that captures the patients’ genomic complexity. Specifically, our project aims are: to optimize (or use) current protocols for differentiation of iPSC into 1) functional hepatocytes and 2) functional endothelial cells; 3) to generate HA patient-specific iPSC lines from carefully selected patients, which will be used for 4) assessing the effectiveness of drugs that promote nonsense codon readthrough for treating HA; 5) investigating the functional significance of missense or potential splice site mutations on F8; and 6) optimizing genetic correction of HA patient-specific iPSC. The consortium is composed by two hospital-affiliated research institutes (VHRI & Molinette), and two higher education Universities (UPO and Paris XI University/INSERM), and will work closely with IBEC (research institute). The consortium partners combine specific leading expertise in clinical and molecular biology of HA, cell reprogramming, differentiation of hepatocytes and endothelial cells, and gene therapy, as well as significant knowledge of all Partners in different aspects of HA research, in order to create bona fide human disease models using the relevant cell types derived from patient-specific iPSC, and strengthening the transnational research cohesion.

Acronym	HEMO-iPS
Project Topic	3rd JOINT CALL FOR RESEARCH PROJECTS ON RARE DISEASES (2011)
Network	E-Rare-2
Call	3rd Joint Call for Research Projects on Rare Diseases

Project partner

Number	Name	Role	Country
1	Vall d'Hebron Research Institute	Coordinator	Spain
2	Inserm	Partner	France
3	Azienda Ospedaliera Universitaria S. Giovanni Battista – Molinette	Partner	Italy
4	Blood and Tissue Bank	Partner	Spain