Dr. Paul Kenna:

I work in the research department of the Royal Victoria Eye and Ear Hospital, which has a long-standing interest in the genetics of inherited retina degeneration. Usher's syndrome is a significant subset of inherited retina degeneration, whereby retina degeneration is combined with hearing loss. I started my genetic work in collaboration with the ocular genetics unit in Trinity College Dublin more than 25 years ago. In 1989, we were the first to identify a gene responsible for any form of retinopathy and since then progress has been much more rapid than I would have predicted.

With advances, particularly in our ability to sequence and identify the building blocks of genes and to identify changes which may be disease-associated, over 205 genes have now been identified in a whole variety of inherited retinal degenerations. The identification of genes responsible for Usher syndrome has been even greater than that. It is estimated that we know 60% to 70% of the genes that may cause inherited retinal degeneration, but in the case of Usher syndrome it is estimated that there are 12 different genes and we know ten of them at the moment. Essentially, therefore, the genetic mystery of Usher syndrome has largely been solved. We can now make genetic diagnosis relatively easily with the newer technologies for identifying disease-associated gene changes.

The research which I and others have been involved in for the past 25 years and longer is now transitioning to becoming a diagnostic test. I would urge that consideration be given to the importance of doing that gene testing, particularly on very young children who have been identified with congenital hearing loss because a significant portion of those will actually turn out to have Usher syndrome. At the moment the visual part of Usher syndrome only comes to light generally when they are in their teenage years or even a little older whereas if the genetic testing could be done as soon as the significant congenital hearing loss is identified, the true diagnosis comes to light and the clinical care pathway which Dr. Cummings commented on, can be started from the outset. Therefore, adaptations to education and so on can be set in motion when they will be of value and before the patient reaches a stage where they have a significant visual problem which, unfortunately, is the way most patients with Usher syndrome come to light at the moment. Their hearing loss is known from a very early age but it is only subsequently that the vision deficit becomes apparent.

Another result from the advance in genetics and the identification of genes responsible for Usher syndrome is that there are realistic prospects in the foreseeable future of that knowledge being used to develop gene-based treatments. There is already one human clinical trial which has just started - we do not have any results, it is in a very early stage - basically replacing the defective gene in patients with a form of Usher syndrome due to the Myosin 7A gene, and replacing the defective copies of that gene with normal copies of the gene with the hope of either stabilising visual function or there may even be a prospect of visual improvement.

There are two clinical trials going on of similar gene replacement in non-syndromic forms of retinitis pigmentosa. In both of those the data would indicate that not only does the gene treatment stabilise the condition, but it actually leads to vision improvement. The same may be the case with Usher syndrome. There will be greater treatment options based on knowledge of what genes are causing particular forms of Usher syndrome. The treatments will very likely be gene-specific, so patients with Usher syndrome will have to know what genes are causing their particular condition.