13 February 2017
ByAppeared in BioNews 888
This technique might eventually be used to treat fetuses affected by Usher syndrome, a genetic condition responsible for three to six percent of childhood deafness, preventing them from being born deaf.
Last week, researchers at Harvard Medical School partially restored the hearing of genetically deaf mice using a separate gene therapy technique (see BioNews 887). Those mice were able to hear sounds at around 70–80 decibels – some mice in the present study could hear sounds as quiet as 25–30 decibels. The treatment also restored the mice's balance, which is affected by the condition.
The mice were genetically engineered to have a mutation in the Ush1c gene, the same gene that causes Usher syndrome. The gene normally produces a protein called harmonin, without which the hair cells in the ear deteriorate.
Previous gene therapy techniques had only been able to penetrate the inner hair cells, but in a separate study in the same issue of Nature Biotechnology, scientists at Harvard demonstrated that they could penetrate 80–90 percent of both inner and outer hair cells, using a synthetic virus to deliver a functional Ush1c gene into the cells.
Using this improved technique, Dr Géléoc was able to treat the deaf mice. 'This strategy is the most effective one we've tested,' she said. '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.'
After treatment the hair cells grew normally, and the effects persisted for at least six months. The mice had to be treated straight after birth or the therapy was not effective. The therapeutic window in humans would likely be in the uterus while the cochlea is still developing.
'This is a very encouraging result … but it is only in a mouse model. One of the biggest risks is that the new synthetic viral vector has not been given to humans yet,' said Professor Alan Boyd, president of the Faculty of Pharmaceutical Medicine, who was not involved in the study. He estimates that human trials are at least three years away.
The researchers say that this approach could be effective for more than 100 genetic disorders that affect hearing in people.