Tel Aviv University (TAU) scientists have produced a scientific breakthrough – gene therapy, proven in lab mice, that could replace defective genes connected to congenital deafness with healthy genes and prevent hearing deficits in children. The treatment for genetic deafness caused by a specific mutation was identified for the first time in Israeli families. 

Gene therapy is a promising strategy to treat genetic deafness. Since the auditory systems of humans and mice are very similar in structure, function, and even gene expression, mice serve as an excellent model for basic and translational auditory research, said the researchers. They injected a healthy gene into the ears of mice with a mutation for deafness, replacing a defective gene in cells that are crucial for hearing. Newborn mice that received this treatment developed with completely normal hearing. Following the successful study, the scientists are currently developing similar therapies for other mutations that cause deafness.

The study, just published in the journal EMBO Molecular Medicine under the title “Neonatal AAV gene therapy rescues hearing in a mouse model of SYNE4 deafness,” was led by Prof. Karen Avraham and Shahar Taiber, a student in the combined MD-PhD track, from the department of human molecular genetics and biochemistry at the TAU’s Sackler Faculty of Medicine, and the Sagol School of Neuroscience, and Prof. Jeffrey Holt from Boston Children’s Hospital and Harvard Medical School. 

Deafness is the most common sensory disability worldwide. According to the World Health Organization, there are about half a billion people with hearing loss in the world today – and this figure is expected to double in the coming decades. One in every 200 children is born with a hearing impairment, and one in every 1,000 is born deaf. In about half of these cases, deafness is caused by a genetic mutation. There are currently about 100 different genes associated with hereditary deafness.  

“In this study we focused on genetic deafness caused by a mutation in the gene SYNE4 – a rare deafness discovered by our lab several years ago in two Israeli families, and since then identified in Turkey and the UK as well,” explained Avraham. “Children inheriting the defective gene from both parents are born with normal hearing, but gradually lose their hearing during childhood. This happens because the mutation causes mislocalization of cell nuclei in the hair cells inside the cochlea of the inner ear, which serve as soundwave receptors and are thus essential for hearing. This defect leads to the degeneration and eventual death of hair cells.”

“We implemented an innovative gene therapy technology: we created a harmless synthetic virus and used it to deliver genetic material – a normal version of the gene that is defective in both the mouse model and the affected human families,” added Taiber. “We injected the virus into the inner ear of the mice, so that it entered the hair cells and released its genetic payload. By so, we repaired the defect in the hair cells, and enabled them to mature and function normally.”

The treatment was administered soon after birth and the mice’s hearing was then monitored using both physiological and behavioral tests. “The findings are most promising,” said Holt. “Treated mice developed normal hearing, with sensitivity almost identical to that of healthy mice who do not have the mutation.” 

Prof. Wade Chien, MD, from the NIDCD/NIH Inner Ear Gene Therapy Program and Johns Hopkins School of Medicine, who was not involved in the study, explains its significance: “This is an important study that shows that inner ear gene therapy can be effectively applied to a mouse model of SYNE4 deafness to rescue hearing. The magnitude of hearing recovery is impressive. This study is a part of a growing body of literature showing that gene therapy can be successfully applied to mouse models of hereditary hearing loss, and it illustrates the enormous potential of gene therapy as a treatment for deafness.”