Gene therapy: a first which reinforces the parents’ hopes of the ELA association
On october 28th was announced at the Congress of the European Society of Gene Therapy in Rotterdam a first in the world : the major medical and scientific breakthrough, carried out by Dr. Nathalie Cartier-Lacave and Pr. Patrick Aubourg, head of the Neurologic Pediatrics Unit and director of the Inserm U745 at the Saint Vincent de Paul Hospital (Paris).
Read the Press release
Gene Therapy for Adrenoleukodystrophy: it’s a first
This gene therapy is for the first time assessed in adrenoleukodystrophy (ALD), a genetic disease linked to the X chromosome. ALD results in the destruction of myelin (sheath around the nerves) in the brain and spinal cord. All the vital functions can be affected.
ALD is the most frequent form of leukodystrophy. It affects nearly 30 % of the cases recorded by the ELA association – representing approximately 35 new cases per year in France – and is at the origin of the association.
These diseases were brought to light thanks to the action of the European Leukodystrophy Association (ELA) and his emblematic supporter, Zinédine Zidane.
The fight against these diseases started in 1992 when a parent, Guy Alba, founding chairman of the ELA association, and Patrick Aubourg, doctor specialist in leukodystrophies in France and in the world, met. The ELA association contributes to the funding of his work since its beginning.
Until now, the treatment of ALD consisted in bone marrow transplant. An approach limited by the scarcity of donors and the risk of rejection. Now, Pr. Aubourg and Dr. Nathalie Cartier, who work on this trial since 1993, chose to test bone marrow autotransplant by " correcting " bone marrow cells before reinjecting them.
A vector derived from the AIDS virus used to introduce the right gene in bone marrow cells: a first in the world
Another innovation: in order to transfer durably the gene into cells, they used a vector not very common derived from the AIDS virus. Indeed, the HIV is the only virus capable of transferring a therapeutic gene into the nucleus of non-dividing cells, like stem cells and neurons, in order for the therapeutic gene to have a long term effect.
A Californian biotech company produced the inactivated lentivirus carrying the missing ALD gene.
Initially, isolation of bone marrow stem cells from the blood of two children was carried out. These cells were then incubated with the inactivated virus in the laboratory of Pr. Marina Cavazzana-Calvo in the Necker Hospital (Paris). After safety tests were approved, cells were reinjected in the blood in the department of Pr. Alain Fischer in the Necker Hospital.
Importance of the first results for ALD, other genetic diseases and non-genetic diseases.
" Preliminary results at 6 months and one year are encouraging because the missing protein is expressed at an important percentage in blood cells and for a long time " say the doctors. "But we need to be cautious, especially we need to know if it will be a sufficient and long term effect and if no complications will arise due to the use of this vector ".
" If confirmed, they could lead to new paths for genetic diseases like sickle cell anemia, thalassemia and cancer in particular", concludes Pr. Aubourg.
Finally, the demonstration is made that the HIV (lentivirus) can be used to transfer a therapeutic gene into cells. Thus opening possibilities for numerous genetic diseases and all the families of the ELA association for whom it was impossible to consider gene therapy with traditional viruses (retrovirus), like for example in the case of children confined to sterile environment (bubbles).
These trials require much more important funds and ELA must largely contribute to it. The immediate needs for the next two tests amount to 600 to 700 000 euros. Within two years, three more patients should be treated. This bone marrow autotransplant could be proposed to all ALD-AMN candidate patients within five years. With the possibility of ALD screening sistematically at birth.
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