Posted on 8 February 2017
An improved gene therapy construct has restored hearing in genetically deaf mice to impressive levels of sensitivityUsher syndrome causes deafness in many children and progressive vision loss too. Mice with a similar mutation in the gene Ush1c are also born with a defective protein called harmonin – leading to a lack of organisation in sensory hair cell bundles that leads to profound deafness and a deterioration of light sensing cells in the retina. A number of promising gene therapy approaches are now being tested for blindness, and previous tests have enabled transfection of inner hair cells in the ear, but not the outer hair cells which are trickier to reach. Now, scientists from Boston Children’s Hospital and Harvard Medical School have designed a new and optimised vector called Anc80 which is able to reach outer hair cells in the cochlear.
“We have shown that Anc80 works remarkably well in terms of infecting cells of interest in the inner ear. Outer hair cells amplify sound, allowing inner hair cells to send a stronger signal to the brain. We now have a system that works well and rescues auditory and vestibular function to a level that’s never been achieved before. With more than 100 genes already known to cause deafness in humans, there are many patients who may eventually benefit from this technology”A solution to genetic deafness? When a corrected version of the Ush1c gene was transported using this Anc80 synthetic vector both the inner and outer hair cells began expressing functional harmonin protein. This quickly led to a normalisation of sensory bundles and began signalling to the brain. By testing if these mice reacted to sudden sounds, they found that 19 of 25 treated mice could hear quieter than 80 decibels, and a select few could even hear below 25-30 decibels, which is similar range to normal mice. Unfortunately the therapy only worked effectively when applied right after birth and not when delayed by 10-12 days, which poses a problem for human application. The research team don’t yet know why a delayed therapy failed to restore hearing and balance. On a positive note, as Usher syndrome affects vision loss too in a more gradual respect, we can be more confident that later treatment would have more hope of success. Treatment of the retina with gene therapy vectors is already progressing much faster than for treatment of the ear, which could mean quicker translation of existing research, Read more at MedicalXpress