And this revival owes much to the new tools used

This is a first: two children of nine and nine and a half years with adrenoleucodistrophy (ALD), a rare brain disease, are to be treated successfully with a method combining cell therapy and gene therapy. More than two years after the start of the treatment, the progression of the disease, stopped a few months after the administration of the treatment, has still not resumed. Two young patients are well and, to date, no side effect has been observé.

This result is the culmination of 16 years of research conducted by Nathalie Cartier-Lacave, Research Director at Inserm, and Patrick Aubourg, Professor of Pediatric Neurology at hôpital Saint-Vincent-de-Paul, University Paris-Descartes. He is also the fruit of a collaboration between Inserm and Assistance publique-Hôpitaux in Paris with the constant support of the leukodystrophies European Association and the French Association against myopathies, organizer of the Telethon.

"Corrected" stem cells

The adrenoleucodistrophy is a hereditary disease due to the malfunctioning of a gene. It results in the destruction in the brain and spinal cord myelin, the fatty membrane which isolates each nervous beam. In children, it occurs between five and seven years and first reaches the brain. In a few years, it causes paralysis and impairment of brain function, and then death. Some 35 new cases are diagnosed each year in France.

So far, the only possible treatment was the bone marrow transplant, which gives good results if it is performed at the first appearance of symptoms. But its use has many limitations such as the difficulty of finding a compatible donor in time, the short period where it is efficient, serious complications in 10 to 20 of cases.

Hence the interest of the alternative method developed by Nathalie Cartier-Lacave and Patrick Aubourg. It is to take in the young patient's own bone marrow cells to correct a functional version of the deficient gene transfer then to he injected back them. "Corrected" cells then earn the bone marrow, then the brain via the blood. Bone marrow cells are the precursors of red blood cells (blood red, platelets, etc.), including macrophages, a subtype, microglia, resides in the brain. These microglia contribute to the proper functioning of brain cells with patients suffering from adrenoleucodistrophy. It is the presence of microglia cells, "corrected" blood strains, that allows to stop the progression of the disease.

New tools

Nathalie Cartier, Patrick Aubourg will now attempt to confirm their good results in starting a new clinical trial with other children and adults, both in France and in the United States. To do this, they are establishing, with the help of Inserm Transfert, an industry partnership. For Patrick Aubourg, "no doubt, in any case, that these results should give a new boost to gene therapy." "For 2009 alone, the major scientific journals have published four articles about success in three different diseases."And this revival owes much to the new tools used. "The lentivirus will be able to be used to treat all hereditary diseases previously treated by bone marrow transplant," he observed. Further progress in the tools could come from two new approaches, developed one by American Sigma Aldrich ("zinc fingers"), the other by French Cellectis ("meganuclease"). They should integrate the gene in the location chosen for the genome, and thus remove the most serious side effects.