Gene Therapy Corrects Defective Structures in Inner Ear, Study Shows

The National Institute on Deafness and Other Communication Disorders (NIDCD) has announced that, for the first time, scientists have used gene therapy to correct defective structures in the inner ears of newborn mice. The mice used in the NIDCD study had a type of hereditary deafness also found in humans.

As explained by the authors in an article published in the October 20, 2015 edition of Molecular Therapy, the small sensory cells of the inner ear, often referred to as “hair cells,” transform sound vibrations into nerve impulses. After sound waves enter the inner ear’s cochlea, they produce waves in a fluid layer. The waves lift the overlying hair cells, and bend the stereocilia—tiny hair-like structures on the hair cell surfaces—by driving them into an overlying membrane. Bending the stereocilia triggers an electrical signal that is sent to the brain and interpreted as sound.

There is currently no way to fix or replace defective hair cells and stereocilia in humans, and these new findings suggest a promising approach to restoring hearing in infants who inherit gene mutations that cause defects in the development of hair cells and stereocilia.

According to the NIDCD, Wade Chien, MD, an otolaryngology surgeon-scientist in its neurotology program, studied newborn mice that inherited a mutated gene for a hair cell protein called whirlin. Both people and mice who inherit mutated whirlin genes have abnormally short, fat stereocilia, arranged in extra rows. Because of the stereocilia abnormalities, these hair cells begin to die off shortly after birth. In humans, the whirlin mutation may cause either deafness or Usher syndrome, in which the mutation causes both deafness and blindness. In normal ears, stereocilia are graded in height to form a staircase-like bundle. The size, organization, and survival of the stereocilia are critical to hearing.

Scientists injected gene therapy via a virus carrying the corrected gene for the whirlin protein into the inner ear of mice with the whirlin mutation (whirler mice). Although the gene therapy had minimal effect on treated adult whirler mice, the scientists found that gene therapy in newborn whirler mice restored stereocilia to their normal length and eliminated some of the extra rows of stereocilia. In addition, more hair cells survived in the treated ear as compared to the untreated ear in the same mouse.

The authors report that whirler mice that received gene therapy demonstrated no improvement in hearing ability when tested one to three months after treatment, so Chien and his research team will next try to determine why correcting the architecture of the stereocilia and improving the survival of the hair cells does not restore hearing ability.

Source: NIDCD, NIH