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EUROFANCOLEN Résumé de rapport

Project ID: 305421
Financé au titre de: FP7-HEALTH
Pays: Spain

Periodic Report Summary 2 - EUROFANCOLEN (Phase I/II Gene Therapy Trial of Fanconi anemia patients with a new Orphan Drug consisting of a lentiviral vector carrying the FANCA gene: A Coordinated International Action)

Project Context and Objectives:
Fanconi anemia (FA) is a rare inherited syndrome characterized by the early development of bone marrow failure and increasing predisposition to cancer with age. Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative therapy for hematopoietic manifestations of FA, although associated with complications arising from myeloablation, graft versus host disease and increased incidence of squamous cell carcinoma. The genetic correction of autologous hematopoietic stem cells (HSC) with lentiviral vectors has been proposed as a safe alternative for the treatment of different genetic diseases affecting mature cells from different tissues and/or committed progenitors of the hematopoietic system. Difficulties in the collection of sufficient numbers of HSC from FA patients and the use of sub-optimal transduction protocols with gammaretroviral vectors limited the success of FA gene therapy trials conducted 10 years ago.
The main goal of this project is to develop an efficient and safe gene therapy of FA is based on two recent innovations: 1) Discovery of potent HSC mobilizers, such as plerixafor, and 2) Development of a new lentiviral vector by members of this Consortium, designed as Orphan Drug by the EC in December 2010.

Project Results:
Progress: Based on more than 200 genetic and hematopoietic studies conducted in hematopoietic samples from FA patients it has been possible to start a clinical trial aiming the collection of plerixafor and figrastim-mobilized CD34+ cells from these patients. Six FA-A patients have been recruited so far in this trial. In four patients that reached threshold numbers of CD34+ cells in peripheral blood, clinically relevant numbers of CD34+ cells were collected in 2-3 apheresis. Using a clinical lot of the therapeutic vector, validation studies of transduction have been concluded using a short in vitro transduction protocol (36h). These results, together with data showing the safe integration pattern of the therapeutic provirus in the genome of Fanca-/- mouse hematopoietic stem cells, facilitated the approval of a gene therapy trial based on the transduction of plerixafor/figrastim-mobilized CD34+ cells followed by the infusion in non conditioned patients.

Potential Impact:
The expected final result of EUROFANCOLEN is the development of a new therapy for Fanconi anemia patients, aiming to prevent the characteristic hematopoietic syndrome of these patients. The proposed gene therapy approach may constitute a unique therapeutic opportunity for patients lacking a suitable donor and a good alternative to current allogeneic transplants.

List of Websites:


Ana Collados Martín-Posadillo, (General Secretary)
Tél.: +34 91 34 66 096
Fax: +34 91 34 66 480
Numéro d'enregistrement: 182149 / Dernière mise à jour le: 2016-05-25
Source d'information: SESAM