Two gene therapies show promise in treating rare genetic deafness

Two clinical studies, trialing different gene therapies, have improved the hearing of children with a rare form of congenital deafness.

Congenital deafness refers to the inability of children to hear from birth, with two to eight percent caused by mutations in the OTOF gene, which leads to a loss of functional otoferlin protein. The protein is necessary for sound transmission from hair cells in the inner ear to the brain. Until now, the only treatment available was a cochlear implant, which allowed children to hear sounds but did not fully restore hearing.

The first study was conducted at Fudan University, Shanghai, China, by a team co-led by Dr Zheng-Yi Chen at the Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston. Dr Chen said 'No treatment could reverse hearing loss. That's why we we're always trying to develop a therapy'.

During a surgical procedure, researchers at Fudan University delivered a functional copy of the OTOF gene to the inner ear using an inactive virus. Because of the large size of the gene, copies had to be divided into two components and delivered separately. Once the virus had inserted the DNA into the target cells, the complete protein was assembled by cellular processes that restored sound transmission to the brain.

The study, published in the Lancet, reports substantial improvements in five out of six children who received the gene therapy, which was first reported last year (see BioNews 1214).

Patients with OTOF mutations are an attractive population for gene therapy, as the hair cells of the cochlea are present but not functional. In other forms of congenital deafness, hair cells die during fetal development or in infancy, posing an additional challenge.

The second study was conducted on an 11-year old patient at the Children's Hospital of Philadelphia (CHOP), Pennsylvania, using a different form of OTOF gene therapy. Similar to the first study, copies of the OTOF gene were administered using an inactivated virus, and were injected along the length of the cochlear so as to be delivered to the hair cells of the cochlea.

The patient, who was born with OTOF gene-mediated hearing loss and was profoundly deaf in both ears, now has improved hearing in the one ear that was treated and can hear for the first time.

'It was a dramatic improvement. His hearing is improved from a state of complete and profound deafness with no sound at all to the level of mild to moderate hearing loss, which you can say is a mild disability. And that's very exciting for us and for everyone.' said Dr John Germiller, who was involved in the procedure at CHOP.

However, people within the deaf community have spoken out against the need for a cure as hearing loss is not life threatening and not viewed by all as a disability. Professor Teresa Blankmeyer Burke, a deaf philosophy and bioethicist at Gallaudet University, Washington DC, told AP that it's important to engage with deaf community members about the prioritisation of gene therapy, 'particularly as this is perceived by many as potentially an existential threat to the flourishing of signing Deaf communities.'

It remains to be established how long the effects of the gene therapies last and whether hearing continues to improve in the children who received it.