A neurobiologist who is profoundly hard of hearing has developed an experimental gene therapy that generates the type of cells that are damaged or missing in deaf animals. Mice embryos were injected with a key developmental gene that led to the production of ear cells that convey sounds to the brain – a scientific first.
“That is sort of the major achievement or milestone that we all had to reach,” says Stanford University cell biologist Stefan Heller, who specialises in hearing research and was not involved in the study.
Milestone though it may be, the advance represents only an incremental step in the search for a treatment to human hearing loss, says lead author John Brigande of Oregon Health and Science University in Portland.
“We’re really far away from a cure for deafness,” says Brigande, who began losing his own hearing aged 10 and now hears nothing out of his left ear and only poorly out of his right. He spoke to New Scientist with the help of a closed captioning program.
“I’d like to hear, and I would love to be a member of the research team or community that does define an efficacious therapy, but I think it needs to be approached with enormous caution,” he says.
According to the World Health Organization, some 278 million people suffer from moderate to profound hearing loss, which is generally caused by damage to the cochlea’s “hair” cells. Loud sounds, antibiotic drugs and gene mutations can all deaden these cells, which convert the air vibrations of sound into the electric currents used by the brain.
Other research teams have regenerated hair cells in mice and guinea pigs that had been deafened by drugs, but that means their regained hearing could have been down to cells spared by the drug, Brigande says.
To check this explanation, his team worked with mice that could hear and focused on birthing new hair cells, not restoring hearing. They achieved this feat by injecting mice embryos with a gene called Atoh1, as well as a gene that produced a fluorescent protein.
Atoh1 seems to be a hair cell master switch that activates myriad genes that turn developing cells into hair cells, Brigande explains. Newborn mice that received the gene therapy grew fluorescent green hair cells in precisely the right location in their cochleae, and the cells made connections to nerve fibres that travel to the brain.
More importantly, he and colleague Anthony Ricci proved that the cells worked, converting movements into electrical nerve pulses.
Yet Brigande cautions against over-interpreting such results. His team tested the cells just a few days after birth, and they could have stopped working not long after, he says. They also hope to test the same approach in mice born without working hair cells.
Moreover, Brigande views his team’s research as a useful lab technique, not a potential cure for deafness. “No human subject committee would allow this kind of experiment to be done,” agrees Heller, given the process would involve injecting a foetus with a foreign gene.
The new technique will however allow scientists to tweak other genes potentially involved in hair cell generation, and test the effect in an animal.
“I definitely want to be able to do this in my lab, and a number of other labs will try to set this up as well,” says Matthew Kelley, a developmental neuroscientist at the National Institute on Deafness and other Communication Disorders in Bethesda, Maryland.
The work could well speed the development of a genuine treatment for hearing loss, says Heller, who has investigated the potential for stem cells to treat deafness.
The understanding gained from the ability to tweak the developing mouse cochleae might eventually allow researchers to figure out how to treat deafness with drugs, not untested and controversial therapies such as genes and stem cells. “I think it’s potentially achievable one day,” Brigande says.
Journal reference: Nature (DOI: 10.1038/nature07265)