Gene therapy for the treatment of blindness
Retinal pigment degeneration is a hereditary disease that is one of the main causes of blindness both at a young and old age.
Scientists at the University of Florida, working under the guidance of Professor Gustavo Aguirre, recently completed the first clinical study of a gene therapy method aimed at restoring vision to patients with Leber congenital amaurosis. This disease, characterized by damage to the inner lining of the eye, is diagnosed in about 5% of patients with retinal pigment degeneration.
The new method of gene therapy developed by the authors is intended for the treatment of another form of hereditary blindness linked to the sexual X-chromosome form of retinal pigment degeneration transmitted to sons from carrier mothers. This most common form of the disease manifests itself, as a rule, already at an early age, although boys carrying the defective gene are often born sighted. The onset of the disease is characterized by the loss of peripheral vision and the ability to see in the dark, gradually turning into so-called "tunnel vision" and complete blindness.
The essence of the method is the introduction into the cells of the eye of a working copy of the RPGR gene (retinitis pigmentosa GTPase regulator), responsible for the synthesis of protein necessary for the normal functioning of photosensitive retinal cells – rods and cones, the death of which is the cause of the symptoms of the disease.
Researchers have constructed a viral vector containing not only a "healthy" gene, but also a genetic "switch" that activates this gene after its delivery to the target cell. After successful laboratory tests, they tested the developed approach on dogs with two variants of RPGR gene mutations (dogs, like humans, suffer from both this form of hereditary blindness and Leber's amaurosis, the treatment method of which was also tested on sick dogs). These mutations trigger different mechanisms, ultimately leading to the same result – blindness.
Once introduced into the subretinal space (under the retina), viral vectors strictly selectively penetrated into target cells, which led to structural and functional restoration of the retina. The improvement of the condition of the animals' retina was confirmed using a set of methods traditionally used in the clinic, including electroretinography and optical coherence tomography.
According to the researchers, the uniqueness of the approach lies in the simultaneous restoration of rods and cones. In addition, such manipulations have never been performed on large animal models before. At the same time, gene therapy allows not only to prevent the occurrence of damage, but also to restore the preserved photoreceptors to a normal state. Moreover, the authors demonstrated that the approach also promotes the restoration of contacts of photoreceptors with retinal neurons that send visual signals to the brain.
The scientists plan to conduct a second, larger and longer study and develop a human-safe version of the viral vector. This will make it possible to conduct clinical trials, the results of which, judging by the similarity of dogs and humans in terms of the anatomy and physiology of the eye, the characteristics of the disease and reactions to gene therapy, should be positive.
Article by William A. Beltran et al. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa is published in the on-line version of the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Florida: UF researchers develop gene therapy that could correct a common form of blindness.
Portal "Eternal youth" http://vechnayamolodost.ru
27.01.2012