The IMO Foundation has begun pioneering basic research into the identification of new genes involved in certain retinal dystrophies. This is to involve analysing the genes linked to some of these diseases, where their relationship with other dystrophies has not yet been studied. To do so, IMO research team is to develop a powerful new genotyping tool that will allow for the expansion and thorough, combined study of the 200 genes already known to cause retinal dystrophies, among which it is suspected that the 40% of those causing other dystrophies, with which they have not yet been linked, are very likely "hiding." Should it give satisfactory results, this strategy will be a revolution in the genetic diagnosis of retinal dystrophies, as until now only the groups of genes described as causing each dystrophy could be analysed separately. “It is known, for example, that there are around 30 genes involved in rod-cone dystrophy. If the clinical diagnosis determines that a patient has this type of dystrophy, research into the molecular basis of the condition will focus on these 30 genes. However, the altered gene may not be among them, as we know that there are more genes involved in these dystrophies that have not yet been identified. In this case, no genetic diagnosis of that patient can be given at present, and the only alternative would be to analyse the 25,000 genes of the genome, which is vast,” explains Dr Esther Pomares, head of IMO Genetics Department and research manager.
The new tool, on which the team of geneticists at IMO has started to work, will overcome this barrier, making it possible to analyse the entire group of genes involved in dystrophies and not just those described at present as causing one of them. This new strategy is based on increasingly more evident knowledge that a given gene – of among these 200 – causes different dystrophies, depending on the type of alteration shown. “There are a lot of shared genes among retinal dystrophies. Therefore, these 200 genes are decisive when triggering these conditions, and the genes yet to be located are very likely among them. Many of these missing genes are already identified for certain dystrophies but not for others,” concludes Dra. Pomares. Furthermore, according to the researcher, “by analysing the genes related to all dystrophies together and not just to a specific one, we are able to overcome possible problems in current genetic diagnosis, such as when the ophthalmologist is unable to precisely diagnose the dystrophy in question, as some are very similar to each other, because in advanced stages they have symptoms that can overlap. In this sense, a relatively unclear clinical diagnosis can give us the wrong clue, leading us to study an incorrect group of genes.”
The new method of analysis promoted by IMO research team will also prevent errors in the inheritance pattern, another factor that also determines which genes to research when making a genetic diagnosis. More importantly, it will mean that new, very minority dystrophy genes that are not usually specifically researched can be located. Through this study, the start-up of which has been funded by a patient affected by a retinal dystrophy, IMO Foundation hopes to find new genes involved in some of these conditions and to assess a new diagnostic strategy that will allow for these diseases to be diagnosed in a more complete manner. For Dr Esther Pomares, “genetic analysis in these cases is crucial, as it is the only tool that can guarantee a reliable, definitive diagnosis at present.”
Foundations for genetic therapies
Furthermore, according to the geneticist, “the basic research is a fundamental initial step, as it lays the foundations for the development of future, long-awaited treatments in conditions such as these, which have no cure at present.” Certain genetic therapies that, through a single transport vector or through nanoparticles, introduce an artificially synthesised gene into the affected cells to perform the duties of the altered gene are currently at a very advanced stage. This prevents the loss of vision caused by retinopathies from advancing, although it does not allow for vision to be recovered, as the lost cells are not regenerated. “These therapies are, therefore, particularly effective during the initial stages of the disease,” explains IMO specialist. The study, titled Identification of new retinal dystrophy genes, which is to last for an estimated 18 months, is currently in a preliminary phase in search of 20 candidate families of patients with prior genetic diagnosis, whose known genes for the diagnosed dystrophy have been ruled out.
Retinal dystrophies are a heterogeneous group of hereditary diseases that, due to their low prevalence, are included in the group of so-called “rare diseases.” They all cause an anatomic alteration of the retina, leading to severe loss of vision. They currently have no cure and, therefore, being able to perform a genetic diagnosis of each one is essential in laying the foundations for the development and application of gene therapies over forthcoming years, thus stopping loss of vision in patients. Despite generally not being very prevalent, the most widespread are retinitis pigmentosa (which affects 1 in every 4,000 people), Stargardt disease, rod-cone dystrophy and macular dystrophy.