Objective
Research, develop and produce innovative gene and cell therapy treatments for rare genetic diseases.
www.genethon.fr

Means
• Exploratory research into six major themes: immunology and gene therapy, limb-girdle dystrophy, degeneration and cell survival, integration and chromatin context, vectorisation, administration and physicochemistry, imagery/cytometry.
• Translational research, and preclinical and clinical development: gene transfer, preclinical and clinical studies, viral and immunological safety.
• Development of pharmaceutical bioprocesses, analytical controls.
• Production via the Cell and Gene Therapy Establishment (CGTE): two GMP (Good Manufacturing Practices) vector drug production sites for the manufacturing and release of clinical batches (1 900m²).
• Regulatory affairs, quality assurance and valorisation.
• Technological plateaux: DNA and cell bank, imagery and in vivo evaluation.
• Clinical projects for rare diseases, exploring three different therapeutic strategies:
- in vivo gene therapy from an AAV vector for neuromuscular diseases (limb-girdle and Duchenne muscular dystrophies), respectively by gene transfer or gene surgery (exon skipping)
- ex vivo gene therapy from a lentiviral vector (Wiskott-Aldrich disease).
• Several other exploratory research projects are likely to proceed to clinical development in the years to come (alphasarcoglycanopathy, dysferlinopathy etc).
Généthon projects are evaluated annually according to the following procedures: submission of reports, evaluation and follow-up committees, hearings, with financing decisions being taken by the board of governors of the AFM after consultation with the permanent committee of the Scientific Council.

Key figures 2007
10 000 m² – 220 personnel – 44 publications – 3 patents registered.

Financing 2007
21.2 million euros.

Highlights of 2007
• Continuation of the phase I gene therapy trial for gamma-sarcoglycanopathy led by Prof Serge Herson (Pitié-Salpêtrière Hospital) in partnership with the Institute of Myology. Three patients included (out of six).
• Following a second inspection, confirmation of Afssaps (French Health Products Safety Agency) accreditation for the second vector and cell production site to GMP norms, through the CGTE.
• Production of vector batches for an Inclusion Body Myositis trial (Prof Klatzmann (Pitié-Salpêtrière Hospital), calpain project (Généthon), cell banks for AAV vector production by baculovirus etc.

Prospects
• Continuation of development of therapeutic projects: 2 requests for authorisation of clinical trials should be registered with Afssaps in 2008-2009
• Development a GMP pre-industrial scale production site: Gamma 2 project (2010)
• Continuation of implementation of innovative research (emergence of new therapeutic projects).

Partners
- France: CNRS, Inserm, University of Evry, Génopole, Necker Hospital, Institute of Myology, University Hospitals of Marseille and Nice, Cochin Institute, Transgène, Gustave-Roussy Institute, ENVA Maisons-Alfort, Pasteur Institute etc. 
- International: Cell Genesys, Viromed, Tiget, HSR San Rafaele, Veneto Eye Bank Foundation, University Hospital of Lausanne, London Hospital, University College of London, Massachussetts General Hospital etc.

History of Généthon – summary of the highlights

Généthon I
Provide researchers with the tools to speed up gene discovery – that was the primary mission of Généthon, created by the AFM in 1990.
A mission crowned with success two years later: in 1992 Généthon I published genome maps six years ahead of the most optimistic forecasts and made the data available to the international scientific community. Généthon’s genetic map was published in three versions (1992-1993-1996) over the period 1990-1996. In 1996 it consisted of 5 264 markers. Sequenced fragments of the human genome could be assembled from this map, which was first published in 2000. The sequencing was completed in 2003.

Généthon II
Still with patients’ benefit as its priority, in 1995 Généthon II took over from Généthon I to exploit the latter’s successes in genetic mapping. Thanks to international cooperation, new instruments were added to the existing technical arsenal, including a radiation hybrid map published in 1996 which allowed the localisation of 30 000 genes. A genotyping department open to outside users was then set up. At the time, these genotyping techniques were among the most efficient in the world, carrying out more than 150 000 genotypes per month.

Généthon III
By a progressive disengagement from sequencing and genotyping activities and a transfer of Généthon’s know-how to the State, the AFM was in a position to focus on the era of therapeutics. Généthon III is entirely devoted to the development of therapeutics.
The laboratory has become progressively more structured and enriched by new teams – particularly experts in regulatory affairs – in order that its own innovations can be brought to the clinical stage in the best possible conditions.
In 2005 Généthon acquired a clinical quality vector unit. This capacity to produce clinical batches remains a guarantee that Généthon will be in a position to exercise control over the whole process in terms of price, delivery time and vector conformity as well as having a new remunerative activity at its disposal.

Généthon IV
Fifteen years after its creation by the AFM in 1990, Généthon IV is at present the main not-for-profit European biotechnology company. It is capable of producing vector batches for clinical trials and possesses know-how unique in France.
Thus, in 2005 Généthon obtained a GMP (Good Manufacturing Processes) accreditation for a part of its premises, which authorised – among other things – the manufacture of gene and cell therapy products (in particular AAV vectors) destined for clinical trials. Thus, these premises take the formal nomination “cell and gene therapy establishment” (CGTE).
Today Généthon is therefore autonomous, with its own production capacity for its strategic projects. This accreditation validates the research policy carried out by the AFM and Généthon, which is to obtain the means to proceed to the clinical phases.
On 28 June 2006 the Cell and Gene Therapy Establishment (CGTE) at Généthon ceertified and released its first batch of  AAV2/1 Gamma-Sarcoglycan, produced by the Harvard Medical School (Boston) and transferred “in bulk” to Généthon, where its production was finalised for a clinical trial in humans.
Thus for Généthon, 2006 marked the beginning of the first gene therapy clinical trial for gamma-sarcoglycanopathy.
Also in 2006 Généthon obtained orphan product designation for calpain 3.

Généthon V
Généthon V is a small-scale pharmaceutical company.
It is an organisation which incorporates research, development and clinical production.
It brings together essential expertise and competences (researchers, physicians, pharmacists, technicians, computer scientists, coordinators and statisticians) from exploratory research to clinical drug administration.
At present, four programmes for 4 therapeutic products have received orphan product designation (gamma-sarcoglycanopathy, calpainopathy, Duchenne and Wiskott-Aldrich muscular dystrophies). One clinical trial is under way.