> Immunodeficiencies
In Milan (Italy) a team supported by the French and Italian Téléthons is preparing to file the first marketing authorisation for a gene therapy concerning an immune deficiency. The 10 children treated during the preliminary trial are now out of their sterile bubbles and able to lead normal lives.

> Skin disease
Still in Italy and thanks to the French and Italian Téléthons, gene therapy has also proved its worth on a rare disease that causes severe skin lesions – junctional epidermolysis bullosa. Cells taken from the palm of a patient were treated with the gene-drug, then cultured and grafted onto his legs, where the epidermis regained its normal state. Now physicians are envisaging the replacement of the whole of the patient’s skin, step by step.

> Exon-skipping
This gene therapy technique consists of undertaking real gene surgery in order to restore protein production. An AFM-supported phase I trial carried out by the biotechnology company Prosensa and the University of Leiden Medical Centre (Netherlands) demonstrated the feasibility and tolerance of exon skipping by oligonucleotides in four Duchenne myopathy children. The next step in the programme concerns a phase I trial using a new mode of administration so as to allow treatment distribution to the whole of the body. In France, after the first significant results on the mouse and dog – the largest animal – a trial on humans is in preparation.

> X-linked adrenoleukodystrophy
In October Professor Aubourg (Inserm/Saint-Vincent-de-Paul Hospital, Paris) presented the preliminary results of his gene therapy trial in X-linked adrenoleukodystrophy , begun on two patients in 2006. These results show stable protein expression, but need to be reinforced by the inclusion of new patients in order to validate the long-term non-toxicity of the vector and stability the therapeutic gene expression.

> With stem cells from bone marrow
This is the strategy of the phase I/II trial coordinated by Patricia Lemarchand at the University Hospital of Nantes. Begun in December 2004, this trial consists of injecting stem cells from their own bone marrow into heart attack victims in the hope that these cells will proliferate and encourage the regeneration of the damaged zone of the heart. This study is also trying to determine which patient group would be most receptive to this form of treatment. One hundred patients have been treated during this trial, whose results are expected in 2008.

> With embryonic stem cells
This is a strategy which has just proved its usefulness and feasibility: human embryonic stem cells can differentiate themselves into cardiac cells and regenerate the failing hearts of rats. This represents a great hope for the treatment of heart failure, whether due to a common coronary attack or a rare disease. These results were obtained by the team of Michel Pucéat from I-Stem, the laboratory partly founded by the AFM and which specialises in stem cells.

> For Friedreich Ataxia
This rare hereditary neurodegenerative disease is due to an abnormal accumulation of iron in certain regions of the brain. It is manifested by problems of the control of movement, balance, gait, diction and eye movement. Occasionally, this is associated with cardiomyopathy. Thanks to Téléthon support, a team from the Necker-Sick Children’s Hospital in Paris has tested a molecule, trapping the iron in nine patients. The result was positive: eight out of the nine experienced improvement in movement coordination, balance, walking and other neurological disorders.

> For spinal amyotrophy
This rare hereditary neuromuscular disease is due to the degeneration of certain nerve cells of the bone marrow – motoneurons. As no order for muscular movement is received, the muscles weaken, atrophy and contract. A clinical trial has just begun on twenty patients to test the absorption and elimination speeds of TRO19622, a new molecule developed by the biopharmaceutical company Trophos and granted orphan medicinal product status by the European Commission. Over the last seven years Trophos has been receiving decisive financial support from the AFM, thanks to Téléthon donations.