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.

The Netherlands
Genetics and pathogenesis of chronic granulomatous disease and development of new gene transfer therapeutic approaches

Project Coordinator

Fondazione Centro San raffaele del Monte Tabor HSR-TIGET


Dirk Roos Sanquin Research and University of Amsterdam Blood Cell Research Amsterdam, The Netherlands
M. Yavuz Köker University of Erciyes Immunology laboratory, Cappadocia Transplant Centre, Hematology-Immunology division Kayseri, Turkey
Manuel Grez Institute for Biomedical Research - Georg-Speyer-Haus Applied Virology and Gene Therapy Frankfurt, Germany
Paolo Rossi IRCCS Ospedale Pediatrico Bambino Gesù Medicina Pediatrica Rome, Italy
Paul J. Coffer University Medical Center Molecular Immunology Lab Department of Immunology & Pediatrics Ultrech, The Netherlands

Publications of the EURO-CGD project

Major results of the project

Chronic granulomatous disease (CGD) is am immune deficiency characterized by a severe defect in the function of the phagocytes, a particular type of white blood cells. Patients with CGD are highly susceptible to bacterial and fungi infections, which occur in many organs. Due an increased inflammatory response patients also undergo formation of granulomas in tissues. Despite the extensive use of antibiotic and improvements in bone marrow transplant procedures, treatment of CGD remains challenging. The first objectives of this project were to provide more information on the mechanisms that cause the disease alterations and immune deficiency, also taking into account different gene defects found in patients. The other goal was to develop novel therapeutic approaches based on gene therapy with blood stem cells.

We studied in depth more than 100 European patients affected by CGD, particularly from Turkey and Italy. We obtained important information on the genetic, biochemical and clinical features of these patients and the different disease variants. Immunological studies allowed us to better clarify the role of other cells of the immune systems, in addition to phagocytes. We found that both T cells and B lymphocytes can contribute to cause disease manifestations. Finally, we designed and tested a novel gene therapy approach for the treatment of the X- linked form of CGD using HIV-derived vectors. Preclinical studies have been successfully completed and we are moving to clinical trials using gene corrected patients blood stem cells. Overall, our results have improved our understanding of the disease and have allowed us to bring to clinical applications novel gene therapy approaches for CGD.

E-Rare 2012 - Created by Toussaint Biger