A team of French researchers has used a new genetic therapy to give back the sense of vision to several blind dogs affected by a rare genetic condition known as Leber's Congenital Amaurosis. This genetic condition, which affects between 1,000 and 2,000 children in France alone, leads to blindness shortly after birth. In this Inserm news release (PDF format, in French), you'll discover how the scientists managed to restore sight for 7 of the 8 dogs they've treated. Now, they envision clinical trials on humans, but not before several years. Read more...
As I'm not specialized in genetics, I just want to give you some short facts about the Leber's condition. It is known that it is caused by mutations affecting eight genes, including the RPE65 one -- RPE meaning Retinal Pigment Epithelium.
According to what I've read, this RPE65 gene codes a protein which carries the same name, and which plays a critical role in retinoid processing and in the synthesis of rhodopsine. The French team has injected a 'promoter' of this deficient gene inside the cells of the retinal pigment epithelium to eight dogs affected by the Leber's condition. And seven of these dogs have recovered their sight.
Now, let's turn to some pictures taken two weeks after this injection. On the photo below, the untreated eye of one of the dogs is covered. So the dog sees with its 'repaired' eye. (Credit: Inserm/Gene Therapy)
On this second picture, you can see that the dog has achieved a difficult course in about 7 seconds (Credit: Inserm/Gene Therapy). When the other eye is covered, the dog is blind and confused and it needs more than a minute to achieve the same course. Here is a link to the short movie from which these images have been extracted.
This research was published online by the Gene Therapy scientific journal under the name "Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium" (October 5, 2006). Here are some selected -- and simplified -- excerpts from the abstract.
The purpose of our study was to evaluate [a AAV (adeno-associated virus)] vector [...] for the ability to restore vision in purebred Briard dogs and to assess the safety of gene transfer with respect to retinal morphology and function.
Although fluorescein angiography and optical coherence tomography examinations displayed retinal abnormalities in treated retinas, electrophysiological analysis demonstrated that restoration of rod and cone photoreceptor function started as soon as 15 days post-injection, reaching maximal function at 3 months post-injection, and remaining stable thereafter in all animals treated at 8–11 months of age.
As the oldest dog treated -- 30 months -- didn't recover vision, this probably indicate that this genetic therapy should start when subjects are still young enough to still possess 'active' photoreceptors in their retina.
Finally, as reports the Association Française contre les Myopathies (AFM) this research work opens the way to human clinical trials (in French), but probably not before several years. You'll also be able to watch several videos on the AFM site, including one of a 22-year-old dog suffering from this congenital disease.
Sources: Inserm news release, October 5, 2006; and various websites
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