Skip to main content

Phase I/II ex vivo gene therapy clinical trial for recessive dystrophic epidermolysis bullosa using skin equivalent grafts genetically corrected with a COL7A1-encoding SIN retroviral vector

Objective

RDEB is one of the most severe rare genetic skin diseases of children and adults characterized by skin blistering resulting from lack of expression of type VII collagen. There is no treatment for this life-threatening disease. In March 2009, we obtained the orphan drug designation for the Medicinal product: “Skin equivalent graft genetically corrected with a COL7A1-encoding SIN retroviral vector”, which was developed during the THERAPEUSKIN project (FP6) to treat RDEB patients by ex vivo gene therapy. This approach uses autologous skin grafts made of primary keratinocytes and fibroblasts genetically corrected with a safe (SIN) retroviral vector expressing type VII collagen under the control of the EF1alpha promoter. We have demonstrated the feasibility of the approach in pre-clinical studies in mice and the absence of tumorigenicity. We now aim at preparing and undertaking a first clinical trial in 3 selected RDEB patients.
This project will involve the transfer and the adaptation from the research laboratory to clinic, of the entire experimental procedure for genetic correction of RDEB skin equivalents suitable for transplantation in patients. This will include validation of the viral pilot batches and the GMP viral vector lot, the establishment of SOPs,
the identification and selection of the best GMP culture system and the scale-up of the graft preparation. A clinical-grade cell bank of primary keratinocytes and fibroblasts will be established from 3 selected RDEB patients who are tolerant towards type VII collagen. Determination of transgene integrity, analysis of the proliferative capacities of transduced keratinocytes and the level of type VII collagen expression will be assessed. Safety assessment will include tumorigenicity assays, survey of grafted genetically corrected skin and integration site analysis. The regulatory and safety issues of these procedures related to the preparation of
clinical grade genetically modified cells suitable for human transplantation will be addressed. Authorization of the clinical trial by the AFSSAPS will allow the first patients to be treated and followed up. This “bench to bedside” project will serve as a proof of principle of safe gene therapy for RDEB. It has the potential to bring clinical improvement to these young patients and to represent a significant progress in the treatment of this devastating skin disease.

Field of science

  • /medical and health sciences/basic medicine/pharmacology and pharmacy/pharmaceutical drug
  • /medical and health sciences/clinical medicine/transplantation
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy

Call for proposal

FP7-HEALTH-2010-single-stage
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 1 811 916,56
Administrative Contact
Nicolas Jeanjean (Mr.)

Participants (9)

ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
EU contribution
€ 180 000
Address
3 Avenue Victoria
75000 Paris
Activity type
Research Organisations
Administrative Contact
Dauvergne Agnès (Ms.)
KING'S COLLEGE LONDON
United Kingdom
EU contribution
€ 276 000
Address
Strand
WC2R 2LS London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Paul Labbett (Mr.)
BIONTECH INNOVATIVE MANUFACTURING SERVICES GMBH
Germany
EU contribution
€ 516 203
Address
Vollmersbachstrasse 66
55743 Idar Oberstein
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Klaus Kühlcke (Dr.)
ASSOCIATION GENETHON
France
EU contribution
€ 331 158
Address
Rue De L Internationale 1 Bis
91002 Evry
Activity type
Research Organisations
Administrative Contact
Jean-Philippe Marin (Mr.)
INSERM TRANSFERT SA
France
EU contribution
€ 420 000
Address
Rue Watt 7
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Louis Jammayrac (Mr.)
DEBRA INTERNATIONAL GLOBALES EPIDERMOLYSIS BULLOSA SELBSTHILFE-NETZWERK VEREIN
Austria
EU contribution
€ 30 000
Address
Am Heumarkt 27/3
1030 Wien
Activity type
Research Organisations
Administrative Contact
John Richard William Dart (Mr.)
UNIVERSITA DEGLI STUDI DI MODENA E REGGIO EMILIA

Participation ended

Italy
EU contribution
€ 529 187,94
Address
Via Universita 4
41121 Modena
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Maria Cristina Notarsanto (Ms.)
UNIVERSIDAD CARLOS III DE MADRID
Spain
EU contribution
€ 169 681
Address
Calle Madrid 126
28903 Getafe (Madrid)
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Regina García Beato (Mrs.)
FUNDACION PARA LA INVESTIGACION BIOMEDICA HOSPITAL INFANTIL UNIVERSITARIO NINO JESUS
Spain
EU contribution
€ 697 507,50
Address
Avenida Menendez Pelayo 65
28009 Madrid
Activity type
Research Organisations
Administrative Contact
Juan Ignacio De Juan (Mr.)