Vision diseases: a first trial on 9 patients
It is to treat a rare disease of the retina, congenital Leber’s amaurosis, that a first trial of gene therapy has been carried out. After spectacular results obtained in dogs which have recovered their sight.
The principle : Inject a harmless virus containing the healthy gene under the retina of one eye. A single injection could lead to a lasting action. But we must act as soon as possible so that there are enough photoreceptor cells left.
Where are we at? The trial began in October 2011 in the ophthalmology department of the Nantes University Hospital. It is planned on 9 patients who will receive different doses in order to determine the best tolerated. The principle can then be used for other eye diseases. It is conceivable, for example, to introduce a gene to promote or reduce the vascularization of the artery of the retina, disturbed in age-related blindness or in AMD.
Immune deficits: already healed children
12 years ago, the first gene therapy trial involved a type of immune deficiency (Xscid) that forced children to live in sterile “bubbles”. This treatment, which has since evolved, now makes it possible to save these children. And another type of immune deficiency (ADAscid) is being tested.
The principle : stem cells are taken from the blood cells in the bone marrow, the genetic defect (an abnormal gene in white blood cells) is corrected, and the child is perfused with the corrected cells. A little chemo is necessary beforehand to make room for the cells that are being perfused.
Where are we at? More than 60 children with these immune deficiencies have been successfully treated with this technique, made possible thanks to the support of the French and Italian Telethons. The GSK laboratory has taken an interest in this and is preparing a dossier with a view to obtaining a European MA. A trial also concerns another immune deficiency, Wiskott-Aldrich syndrome, simultaneously in Paris, London and the United States. It is led by Généthon, the AFM-Téléton laboratory.
Duchenne muscular dystrophy: several ongoing trials
No less than 5 so-called “exon skipping” trials are underway in the world for this neuromuscular disease. It comes from a genetic defect that prevents it from making a necessary protein, dystrophin, in muscle. The AFM was involved from the start by supporting research and until its clinical application, notably with a Dutch biotechnology company to which the GSK laboratory is now linked.
The principle : here, we do not correct the deficient gene. Synthetic molecules are injected into the blood or muscle that causes muscle cells to make a functional form of dystrophin.
Where are we at? Several hundred patients have already received this molecule. A trial is testing the safety and efficacy of a treatment injected into the skin every week for one year. Another, with a different dosage, is more advanced. Most of these trials are international. A “real” gene therapy is also being studied in animal models. First human trials scheduled for early 2014.
Brain diseases: we could slow their progression
In adenoleukodystrophy, an abnormality carried by blood cells causes a deficit in the maturation of neurons in the brain. The responsible gene was identified in 1993 in particular thanks to funds collected by the Telethon. And a gene therapy trial is underway.
The principle : The defect is corrected on the affected blood cells, taken from the bone marrow. And we inject them back into the patient.
Where are we at? The first results show that we are able to stop the progression of the disease. Gene therapy trials are also underway in Sanfillipo disease, which arises from a deficiency in the metabolism of brain nerve cells. But the method used is not the same: it involves injecting directly into the area of the diseased brain a virus which contains the drug gene.
