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Gene Therapy for X-linked Chronic Granulomatous Disease (CGD)

Objective

This project is focused on the clinical development of a new orphan drug that can rapidly become a new treatment option for patients with the X-linked form of chronic granulomatous disease (X-CGD). This rare primary immune deficiency of phagocytes is caused by mutations in the gp91phox gene. Affected patients are highly-susceptible to infections and develop inflammatory granulomas. Several members of the Net4CGD consortium have already attempted hematopoietic gene correction of X-CGD using gp91 gammaretroviral gene transfer vectors. While functional correction and clinical benefit was initially achieved, problems arose, linked to insertional mutagenesis, vector silencing and lack of long-term engraftment. Net4CGD proposes future trials to achieve (i) effective transduction of hematopoietic cells, (ii) physiological expression of the transgene and (iii) long-term engraftment of gene modified cells. A new lentiviral vector (LV) was developed to express gp91phox in myeloid cells. Encouraging results obtained in preclinical studies and through the compassionate treatment of a patient, prompt us to test the LV in a multi-center study in several European centers expert in CGD, under the sponsorship of a rare disease specialist. The tasks include i) Manufacturing clinical grade vector to support clinical studies, ii) Conducting a multi-center phase I/II trial in eligible X-CGD patients, with LV gene-modified autologous hematopoietic stem cells to evaluate the safety and efficacy of the procedure iii) Ensuring high-quality and harmonization of products and procedures to facilitate future product registration iv) Obtaining state-of-the art information on biological efficacy and safety in patients by assessing immune restoration and large-scale integrome data. If positive, this study will be used to register the orphan drug. The treatment is expected to improve patients’ quality of life and will reduce the economical burden of CGD. Results should benefit other RD.

Call for proposal

FP7-HEALTH-2012-INNOVATION-1
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Coordinator

ASSOCIATION GENETHON
Address
Rue De L Internationale 1 Bis
91002 Evry
France
Activity type
Research Organisations
EU contribution
€ 2 250 140
Administrative Contact
Jean-Philippe Marin (Mr.)

Participants (10)

UCL Elizabeth Garrett Anderson Institute for Women’s Health
United Kingdom
EU contribution
€ 449 858
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Greta Borg-Carbott (Ms.)
CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG
Germany
EU contribution
€ 270 000
Address
Paul Ehrlich Strasse 42-44
60596 Frankfurt
Activity type
Research Organisations
Administrative Contact
Robert Dornberger (Mr.)
KLINIKUM DER JOHANN WOLFGANG VON GOETHE UNIVERSITAET
Germany
EU contribution
€ 110 250
Address
Theodor Stern Kai 7
60596 Frankfurt Am Main
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Birgit Rosiejak (Dr.)
University of Zurich
Switzerland
EU contribution
€ 300 000
Address
Ramistrasse 71
8006 Zurich
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Janine Reichenbach (Prof.)
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
EU contribution
€ 350 455
Address
3 Avenue Victoria
75000 Paris
Activity type
Research Organisations
Administrative Contact
Agnès Dauvergne (Ms.)
GENOSAFE SAS
France
EU contribution
€ 852 000
Address
Rue De L'internationale 1
91000 Evry
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Severone Pouillot (Dr.)
BIONTECH INNOVATIVE MANUFACTURING SERVICES GMBH
Germany
EU contribution
€ 751 808
Address
Vollmersbachstrasse 66
55743 Idar Oberstein
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Klaus Kuehlcke (Dr.)
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany
EU contribution
€ 300 000
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Activity type
Research Organisations
Administrative Contact
Ina Krischek (Dr.)
Eurofins Genomics Europe Sequencing GmbH
Germany
EU contribution
€ 240 096
Address
Jakob Stadler Platz 7
78467 Konstanz
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Janet Kenklies (Ms.)
FINOVATIS
France
EU contribution
€ 125 000
Address
Cours Lafayette 68
69003 Lyon
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
David Koubi (Dr.)