Deafness is the most common sensory disability on the planet. According to the World Health Organization, about 500 million people suffer from hearing loss. Most worrying is that this number is expected to double in the coming decades. In almost half of the cases, it is due to a genetic mutation. But according to a new study published in the journal EMBO Molecular Medicine on December 22, researchers have developed a therapy that could change the lives of children born with one of these genetic defects. The treatment is based on genetic input to the cells of the inner ear.
Genetic deafness caused by a mutation in the SYNE4 gene
In this study, scientists from Tel Aviv University (TAU) focused on genetic deafness caused by a mutation in the SYNE4 gene, “a rare deafness discovered by our laboratory a few years ago in two Israeli families, and since then also identified in Turkey and the United Kingdom,” they explained. Children who inherit the defective gene from both parents are born with normal hearing, but gradually lose their hearing during childhood. The mutation causes a mislocation of cell nuclei in the hair cells in the cochlea of the inner ear which act as receptors for sound waves and are essential for hearing. This defect leads to the degeneration and eventual death of the hair cells,” says Professor Karen Avraham of the Department of Human Molecular Genetics and Biochemistry at the Sackler School of Medicine and the Sagol School of Neuroscience at TAU.
Here, the scientists created a “harmless synthetic virus and used it to deliver genetic material of a normal version of the gene that is defective in both the mouse model and the affected human families,” says Shahar Taiber, one of Avraham’s students. They then injected it into the inner ear of mice with a genetic mutation for deafness shortly after birth, so that it “penetrates the hair cells and releases its genetic load. In doing so, we repaired the defect in the hair cells and allowed them to mature and function normally,” says Taiber.
Results: “The treated mice developed normal hearing, with a sensitivity almost identical to that of healthy mice without the mutation,” enthuses Professor Jeffrey Holt of the Children’s Hospital of Boston and Harvard Medical School, who participated in the work.
“This is an important study that shows that gene therapy for the inner ear can be effectively applied to a mouse model with SYNE4 deafness to save the hearing,” says Professor Wade Chien of the NIDCD/NIH Inner Ear Gene Therapy Program and the Johns Hopkins School of Medicine. The degree of hearing recovery is impressive. This study is part of a growing literature showing that gene therapy can be successfully applied to models of mice with hereditary hearing loss, and illustrates the enormous potential of gene therapy as a treatment for deafness,” they conclude.
Scientists are currently developing similar therapies for other mutations that cause deafness. Today, about 100 different genes are associated with hereditary deafness.
Sensorineural and conductive hearing loss
The latter belongs to the family of Sensorineural deafness. In this case, the patient suffers from abnormalities in the conversion of the sound signal into nerve impulses and in the interpretation of this signal by the brain. In addition to the genetic cause, this deafness may be due to Ménière’s disease, to certain drugs toxic to the inner ear, to exposure to intense noises, to trauma or infection of the inner ear, to a cardiovascular problem, to damage to the auditory nerve or, more rarely, to the brain’s auditory pathways.
A distinction is made between sensorineural and conductive hearing loss which is due to a problem in the transmission of the sound signal to the outer ear (the visible part of the ear) or the middle ear (the part between the outer and inner ear). The main causes are a congenital deformity of the ear, mechanical blockage, consequences of middle ear trauma, or degeneration of the middle ear bones (otospongiosis or otosclerosis).