Gene therapy for blindness – when dogged determination pays off!

Leber’s congenital amaurosis is a progressive disorder that affects about 3,000 Americans, and hundreds of thousands worldwide, and causes a progressive loss of vision that usually results in blindness. The disease, for which there has until now been no effective treatment, is caused by a mutation in the encoding RPE65, an enzyme which is crucial to the production of the chemical 11-cis retinal that photoreceptor cells in the eye need so that they can respond to light.

In one of my first posts for Speaking of Research last year I discussed on this blog how two teams of scientists at Moorfields hospital in the UK and the University of Pennsylvania had used gene therapy to introduce a functioning RPE65 gene into the eye of patients with Leber’s congenital amaurosis, and only last month Anna Matynia discussed how this treatment employs adenovirus-based vectors that have been developed through years of research in rodents and dogs. While the results of those trials were promising the benefits to most of the patients were modest, which was not all that surprising since the scientists doing the trials knew from their studies of Briard dogs with naturally occurring mutations in the RPE65 gene that the therapy needed to begin early in the course of the disease for maximum benefit. For this reason, and because the therapy appeared safe in the first adult human trials, the team at Pennsylvania decided to include children with Leber’s congenital amaurosis in their next study group.

Briard Dog

The early results of that study have been announced following publication in the medical journal The Lancet, and as expected the greatest benefits have been seen in the children, one of whose eyesight improved to nearly normal, though adults in the study also experienced significant improvement. While this particular therapy will benefit a relatively small number of patients its success and that of early trials of gene therapy for Parkinson’s disease are an indication how gene therapy, a field of medicine that has seen its fair share of hope and disappointment over the past couple of decades, is maturing as scientists have learned from both animal studies and human trials about how to harness this powerful therapeutic approach.

The insights gained through the study of the Briard dog with naturally occurring mutations in the RPE65 gene are a good example of the increasingly close ties between clinical and veterinary medicine, a collaboration that is exemplified by the Comparative Oncology Trials Program which brings together veterinary and clinical oncologists under the leadership of the National Cancer Institute to study cancers that affects both dogs and humans, with a dozen trails of new anti-cancer medications already underway. In the future such trials may play an important role bridging the gap between in vitro and rodent studies in the lab that rely on a relatively limited range of cancer cell lines and the far more diverse cancers seen in the clinic. It is hardly surprising that antivivisectionist groups are opposed to these trials, as our colleagues at Understanding Animal Research point out they are quite happy to put dogma ahead of dogs, but fortunately the majority of veterinarians have a much more positive attitude to animal research.


Paul Browne