Shedding light on Usher disease therapy
Blindness in USH patients is evident only some years after deafness manifests, commonly leading to misdiagnosis. Children who should have opted for early cochlear transplant, end up going for the eventually less and less efficient visual sign language. The 'Fighting blindness of Usher syndrome: Diagnosis, pathogenesis and retinal treatment' (TREATRUSH) project aims to make early USH diagnosis a reality. This will allow patients to take advantage of cochlear implant and in the future of developing retinal gene therapy. The second phase of the TREATRUSH project has witnessed significant progress. Clinical diagnosis of USH1 has been improved and progress has been made in the understanding of the pathogenesis of the retinopathy of the syndrome. Gene therapy trials for some Usher genes are ready to go. Clinical investigation protocols have been devised for diagnosing USH in children under 1 year of age, who can then avail of a more successful cochlear implantation. Using a novel method, the scientists analysed a cohort of 400 patients Europe-wide to develop a more robust and efficient means of diagnosis in all forms of the disease. Mutant mice have proven to be unsuitable for the study of defective USH1 genes. The researchers therefore used other animal models to show that the Usher 1 proteins are associated with an adhesion belt surrounding the base of the photoreceptor outer segment. This conclusion could be extended to human photoreceptor cells. Expert research teams are working on the gene therapy area, including the United States leader group that first pioneered retinal gene therapy. Viral vectors related to the adeno-associated virus (AAV) are being tested for their safety and transduction efficiency of small therapeutic genes. In addition, a top European industrial group is developing a good manufacturing practice-compliant procedure for large-scale production of AAV vectors for clinical trials. The therapeutic applications of TREATRUSH research are invaluable particularly to USH patients, who suffer from dual sensory disability. Early diagnosis is opening the door to the most sustainable therapies, including gene therapy.