A team of researchers was recently able to restore hearing in mice that had been born deaf. Now, the team has further improved the gene therapy technique. Deaf mice treated with this new method gained nearly perfect hearing. The details are in two papers that were simultaneously published in the journal Nature Biotechnology.
To investigate possible forms of gene therapy for treating genetically-based deafness, scientists from the Harvard Medical School collaborated with the Boston Children’s Hospital. The research team first needed a vector, something that could transfer genes into outer ear hair cells without causing damage. The team focused on adeno-associated viruses, non-pathogenic viruses that are often used to deliver medicine or insert genes. After repeated experiments, the researchers identified a virus called Anc80L65. Anc80L65 has already been used in other forms of research and is known for being able to infect organs without causing more than a mild immune response. The team attempted to use Anc80L65 as a carrier for transferring corrected versions of faulty genes to genetically deaf mice. The mice were suffering from Usher syndrome, a genetic disorder with no cure that causes deafness at birth. The disorder also affects humans, causing both deafness and loss of vision. The mice treated with Anc80L65 gene therapy recovered some of their hearing, a first in gene therapy research.
The research team then improved on their previous work, again focusing on Usher syndrome as a model for studying genetically-based forms of deafness. The disorder is caused by a mutation in the Ush1c gene that produces non-functional harmonin, a protein that plays a large role in hearing. The presence of nonfunctional forms of harmonin eventually leads to disorganized brain signaling and hearing loss. The team used the Anc80L65 vector to deliver a corrected version of the Ush1c gene into the ears of newborn mice. The cochlea, found in the inner ear, began to produce healthy versions of harmonin and the treatment worked even better than expected—all of the mice recovered their hearing to some degree. In fact, many of the mice now had hearing on par with healthy mice and could hear low whispers.
The team’s findings are exciting and show that gene therapy may be able to cure certain types of deafness. Specifically, the team was able to “cure” Usher syndrome in mice. The disorder causes other symptoms in addition to deafness, such as balance problems, and these issues were eliminated in the treated subjects. One limitation of the study was that the treatment only worked when the mice were still babies; there was no way to restore hearing in adult mice. It’s also unknown if this treatment would work on non-rodent animals. The researchers intend to continue their study to better understand the processes involved in correcting genetic disorders such as Usher syndrome.
Landegger et al. A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear. Nature Biotechnology (2017).
Pan et al. Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Nature Biotechnology (2017).