NET4CGD

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

 Coordinatore ASSOCIATION GENETHON 

 Organization address address: RUE DE L INTERNATIONALE 1 BIS
city: EVRY
postcode: 91002

contact info
Titolo: Mr.
Nome: Jean-Philippe
Cognome: Marin
Email: send email
Telefono: 33169472572
Fax: 33169471946

 Nazionalità Coordinatore France [FR]
 Totale costo 8˙302˙977 €
 EC contributo 5˙999˙607 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2012-INNOVATION-1
 Funding Scheme CP-FP
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-12-01   -   2016-11-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    ASSOCIATION GENETHON

 Organization address address: RUE DE L INTERNATIONALE 1 BIS
city: EVRY
postcode: 91002

contact info
Titolo: Mr.
Nome: Jean-Philippe
Cognome: Marin
Email: send email
Telefono: 33169472572
Fax: 33169471946

FR (EVRY) coordinator 2˙250˙140.00
2    GENOSAFE SAS

 Organization address address: RUE DE L'INTERNATIONALE 1
city: EVRY
postcode: 91000

contact info
Titolo: Dr.
Nome: Severone
Cognome: Pouillot
Email: send email
Telefono: 33169474770
Fax: 33169471161

FR (EVRY) participant 852˙000.00
3    EUROPAEISCHES INSTITUT FUER FORSCHUNG UND ENTWICKLUNG VON TRANSPLANTATIONSSTRATEGIEN GMBH

 Organization address address: Vollmersbachstrasse 66
city: IDAR-OBERSTEIN
postcode: 55743

contact info
Titolo: Dr.
Nome: Klaus
Cognome: Kuehlcke
Email: send email
Telefono: 49678198550
Fax: 4967820000000

DE (IDAR-OBERSTEIN) participant 751˙808.00
4    UNIVERSITY COLLEGE LONDON

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Ms.
Nome: Greta
Cognome: Borg-Carbott
Email: send email
Telefono: 442031000000
Fax: 442078000000

UK (LONDON) participant 449˙858.00
5    ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS

 Organization address address: 3 Avenue Victoria
city: PARIS
postcode: 75004

contact info
Titolo: Ms.
Nome: Agnès
Cognome: Dauvergne
Email: send email
Telefono: 33144495613
Fax: 33144494070

FR (PARIS) participant 350˙455.00
6    DEUTSCHES KREBSFORSCHUNGSZENTRUM

 Organization address address: Im Neuenheimer Feld 280
city: HEIDELBERG
postcode: 69120

contact info
Titolo: Dr.
Nome: Ina
Cognome: Krischek
Email: send email
Telefono: 496221000000
Fax: 496221000000

DE (HEIDELBERG) participant 300˙000.00
7    UNIVERSITAET ZUERICH

 Organization address address: Raemistrasse 71
city: ZURICH
postcode: 8006

contact info
Titolo: Prof.
Nome: Janine
Cognome: Reichenbach
Email: send email
Telefono: 41442667341
Fax: 41442667914

CH (ZURICH) participant 300˙000.00
8    CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG

 Organization address address: PAUL EHRLICH STRASSE 42-44
city: FRANKFURT
postcode: 60596

contact info
Titolo: Mr.
Nome: Robert
Cognome: Dornberger
Email: send email
Telefono: 496963000000
Fax: 496963000000

DE (FRANKFURT) participant 270˙000.00
9    GATC BIOTECH AG

 Organization address address: JAKOB STADLER PLATZ 7
city: KONSTANZ
postcode: 78467

contact info
Titolo: Ms.
Nome: Janet
Cognome: Kenklies
Email: send email
Telefono: 4975320000000
Fax: 497532000000

DE (KONSTANZ) participant 240˙096.00
10    FINOVATIS

 Organization address address: COURS LAFAYETTE 68
city: LYON
postcode: 69003

contact info
Titolo: Dr.
Nome: David
Cognome: Koubi
Email: send email
Telefono: 33478547940

FR (LYON) participant 125˙000.00
11    KLINIKUM DER JOHANN WOLFGANG VON GOETHE UNIVERSITAET

 Organization address address: Theodor Stern Kai 7
city: FRANKFURT AM MAIN
postcode: 60590

contact info
Titolo: Dr.
Nome: Birgit
Cognome: Rosiejak
Email: send email
Telefono: 496963000000
Fax: 496963000000

DE (FRANKFURT AM MAIN) participant 110˙250.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

gene    modified    obtaining    encouraging    biological    hsct    disease    patients    outcome    vector    clinical    orphan    transduction    cure    engraftment    benefit    positive    cells    life    mutations    correction    phagocytes    lv    safety    oxidase    matched    drug    rare    chronic    cgd    immune       registration    grade    haematopoietic    center    quality    eligible    phox    nadph    efficacy    patient    gp    linked    trial    transgene    genetic    disorder    hematopoietic    infections    cell    myeloid    lentiviral    stem    data    therapy    expression    transplantation    granulomatous    treatment    granulomas    donor    net   

 Obiettivo del progetto (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.'

Introduzione (Teaser)

Gene therapy can offer a solution where standard treatments fail. The genetic correction of the rare genetic disorder X-linked chronic granulomatous disease (X-CGD) is the subject of the NET4CGD study

Descrizione progetto (Article)

X-CGD is an immunodeficiency disorder associated with the inability of phagocytes to kill invading pathogens due to mutations in the enzyme NADPH oxidase. X-CGD neutrophils are unable to produce reactive oxygen species, leading to intractable infections and granulomas.

Conventional treatment of X-CGD consists of lifelong prophylactic administration of antibacterial and antifungal agents and granulocyte infusions. The only established cure to date is haematopoietic stem cell transplantation (HSCT) with a suitable donor. However, in over 60 % of patients no HLA-matched compatible donor is available, and transplantation of a not fully matched graft renders HSCT a high-risk approach.

As an alternative definitive cure, scientists have pursued gene therapy, an approach that entails the ex vivo genetic correction of patient HSCs and their re-infusion back into the patient. Attempts so far, however, have produced unsatisfactory results.

Seeking to improve the outcome of gene therapy for X-CGD, the EU-funded 'Gene therapy for X-linked chronic granulomatous disease (CGD)' (http://www.net4cgd.eu/ (NET4CGD)) network will develop a novel gene therapy strategy. Using state-of-the-art technology and expertise across Europe, the NET4CGD project has constructed an advanced lentiviral vector that carries the wild-type NADPH oxidase gene. Pre-clinical results are encouraging and show a phagocyte-specific expression of the transgene. The ultimate goal is to achieve effective transduction of haematopoietic cells and long-term engraftment of gene-modified cells.

During NET4CGD, the lentiviral vector has been produced at clinical grade and is currently being tested in a multi-centre phase I/II trial in eligible X-CGD patients. Through integrated efforts, project partners have harmonised procedures and optimised the manufacture of the vector and the final gene-modified cell product.

The clinical trial has been registered at the European Medicines Agency (EMA) and will involve approximately 15 patients. The consortium is in the process of obtaining information on biological efficacy and safety in patients, and is analysing the integration profile of the vector. Preliminary data indicate that transduced patient cells display restored biochemical activity and neutrophil oxidative function at therapeutic levels.

Partners are confident that the advanced NET4CGD gene therapy approach will correct the myeloid defect in X-CGD patients and lead to clinical benefit. A positive outcome of the clinical trial will permit the registration of a new medicinal product for the treatment of X-CGD patients, thereby improving their quality of life and reducing the overall healthcare costs.

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