Restoring Hearing with Gene Therapy

The genetic root of Dam’s hearing loss is a condition known as DFNB9, linked to a mutation in the OTOF gene. This gene is crucial for hearing; it codes for a protein named otoferlin, essential for transmitting sound signals from the inner ear to the brain. Normally, sound waves are captured by the cochlea (often referred to metaphorically as the “snail” due to its shape) in the inner ear, where they are transformed into electrical impulses. These impulses are then relayed by nerve cells to the brain, interpreted as sounds. In individuals with DFNB9, a mutation impairs the production of otoferlin, disrupting the signal transmission, rendering the person deaf. This condition is relatively rare, affecting an estimated 200,000 people worldwide.

DFNB9 draws a lot of attention in gene therapy exploration because it is caused by a singular genetic mutation, with no physical damage requirement, and thus is a relatively simple disorder. Recent studies in Europe, the United States, and China have reported promising outcomes.

The innovative treatment involves injecting a harmless virus, engineered to carry healthy copies of the OTOF gene, directly into the cochlea. This requires a minor procedure to access the inner ear through the eardrum. The virus causes a typical infection, integrating the therapeutic gene it carries into the DNA of the cells within the cochlea, therefore kick-starting the production of otoferlin. However, as the size of the OTOF gene is larger than what the virus may carry, researchers devised a method to split the gene into two segments carried by two different viruses, delivering them simultaneously in a single solution. Even though the two gene halves reach the cellular DNA separately, complete otoferlin production occurs once the expression mechanism works during protein synthesis, successfully transmitting signals generated in the cochlea to the brain.

The gene therapy done in the US is said to yield results in just a couple of days. Dam’s father recounts how, within days of treatment, their daughter first began to discern traffic noises, and after about four months, achieved near-normal hearing capabilities. This swift and profound improvement in a child who had never heard before is hailed as a monumental success.

A parallel study by Harvard Medical School, Massachusetts Eye and Ear Infirmary, and Fudan University Hospital in China observed that 3 out of 6 children, aged between 1 and 7 years, began to hear and speak within 26 weeks post-treatment. The parents, on the other hand, reported that their children started responding to sounds much earlier.

Efforts to treat hearing loss with gene therapy have been ongoing for the last 20 years. Although the gene problem targeted in Dam’s treatment is extremely rare, these first successful treatments could lead to future trials targeting over 150 other genetic mutations known to cause early-onset hearing loss.