Israeli scientists develop breakthrough gene therapy for child deafness

“The findings are most promising: Treated mice developed normal hearing, with sensitivity almost identical to that of healthy mice who do not have the mutation,” Prof. Holt said.

By Idan Zonshine, Jerusalem Post, December 23, 2020

https://www.jpost.com/health-science/israeli-scientists-develop-breakthrough-gene-therapy-for-child-deafness-653021

Prof. Karen Avraham and Shahar Taiber. (photo credit: TEL AVIV UNIVERSITY)

Scientists at Tel Aviv University have developed an innovative treatment which may prevent deafness in children who were born with genetic mutations that cause hearing loss, according to a new study published in the medical journal EMBO Molecular Medicine on Wednesday.

The treatment works by delivering a genetic material in the cells of the inner ear using a harmless synthetic virus, which embeds itself into the cells instead of the genetic defect, enabling them to continue functioning normally.

According to the study, the scientists were able to prevent the gradual deterioration of hearing in mice that had a genetic mutation for deafness. They claim the novel therapy could lead to a breakthrough in treating children born with various mutations that cause hearing loss and, eventually, deafness.

The study 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 Sackler Faculty of Medicine, and the Sagol School of Neuroscience, and Prof. Jeffrey Holt from Boston Children's Hospital and Harvard Medical School.

Two years ago, a TAU team led by Prof. Avraham sent waves through the medical community after announcing they had mapped the genes and signals of the inner-ear, leading many to see this as a promising avenue for the future reversal of several types of hereditary deafness.

Deafness is the most common sensory disability worldwide. According to the World Health Organization there are about half a billion people with hearing loss around 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," said 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," she explained.

Representation of cell nuclei in the hair cells inside the cochlea

Taiber explained the study further, adding that "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."

"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," he said.

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: Treated mice developed normal hearing, with sensitivity almost identical to that of healthy mice who do not have the mutation,” Prof. Holt said.

Following the successful study, the scientists are currently developing similar therapies for other mutations that cause deafness.

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, illuminated its significance, saying that it 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," Chien added.