Amplification of human myogenic stem cells in clinical conditions

Objective

The aim of this network is to synergize expertises from European basic researchers, leaders in their field, and European SMEs specialized in stem cell amplification and in safety of these procedures, to set up conditions for autologous transfer of human stem cells in GMP conditions for the treatment of DMD by exon-skipping. Cell therapy trials in DMD has never fulfilled the promises raised by the early results obtained in mouse models. Several groups have recently demonstrated the possibility of generating a truncated, but functional dystrophin using exon-skipping, by masking splicing sequences with oligonucleotides introduced by either direct or viral transfer.

The direct approach can be used as many times as needed, but is extremely expensive, while the AAV approach allows a large dissemination of the masking sequences, but triggers an immune response to the vector, and therefore can be used only once. Cell therapy can thus be used to target sites which have not been cured by the AAV approach, using autologous cells as vectors which, by fusing with the regenerating fibres of the patient, will bring a functional dystrophin to these fibres.

Myoblasts become progressively exhausted in DMD patients as the disease progresses, while stem cells, such as mesoangioblasts or AC133+, remain intact and functional. However, little is known either about the possibility to transduce these cells with oligonucleotides or vectors for exon-skipping, or the methods that can be used to expand these cells in GMP conditions. The technical and ethical guidelines resulting from this network will enable SMEs to expand stem cells with myogenic potential in GMP conditions for clinical trials in patients with DMD or other neuromuscular diseases. This network is a natural link between MYORES, an existing NoE dedicated to muscle research, and TREAT, an upcoming NoE dedicated to therapeutics (FP6 4th Call, line LSH-2005-2.1.1-7) since it gathers specialists belonging to both NoE.

Fields of science

• medical and health sciences › basic medicine › neurology › muscular dystrophy › duchenne muscular dystrophy
• medical and health sciences › health sciences › public and environmental health › epidemics prevention › immunisation
• medical and health sciences › medical biotechnology › cells technologies › stem cells

Programme(s)

• FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006.

Topic(s)

• LSH-2005-1.2.4-7 - Development and testing of new preventive and therapeutic tools, such as somatic gene and cell therapies (in particular stem cell therapies, for example those on neurological and neuromuscular disorders) and immunotherapies

Call for proposal

FP6-2005-LIFESCIHEALTH-7
See other projects for this call

Funding Scheme

STREP - Specific Targeted Research Project

Coordinator

INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE

Address

101 Rue De Tolbiac
Paris
France

Participants (9)

3H BIOMEDICAL AB

Sweden

Address

Dag Hammarskjölds Väg 34A, Uppsala Science Park
Uppsala

CELLGENIX TECHNOLOGIE TRANSFER GMBH

Germany

Address

Am Flughafen 16
Freiburg

FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR

Italy

Address

Via Olgettina 60
Milan

GENETHON

France

Address

1 Bis Rue De L'internationale'
Evry

GENOSAFE SAS

France

Address

1, Rue Pierre Fontaine
Evry

IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE

United Kingdom

Address

Exhibition Road, South Kensington
London

INSERM-TRANSFERT SA

France

Address

101 Rue De Tolbiac
Paris

UNIVERSITY COLLEGE LONDON

United Kingdom

Address

Gower Street 1
London

UNIVERSITÀ DEGLI STUDI DI MILANO

Italy

Address

Via Festa Del Perdono, 7
Milano