In a groundbreaking study conducted in Fudan, China, and co-led by Harvard Medical School researchers at the Massachusetts Eye and Ear, a novel gene therapy has successfully restored hearing in six children born deaf. The experimental treatment involved injecting a specially designed gene into the ear, offering hope for potential applications in treating other forms of genetic deafness.
The study targeted children between the ages of one and seven suffering from inherited deafness caused by a mutation in the OTOF gene. This gene is responsible for producing the otoferlin protein crucial for transmitting signals from the ear to the brain. The absence of this protein disrupts the transmission of signals, rendering individuals deaf.
Over the 26-week trial period, five out of the six children exhibited signs of improved hearing, with four outcomes described as “robust” by Harvard Medical School. The results, published in the journal Lancet, showcased not only enhanced hearing but also improved speech perception, a critical factor in language learning.
Co-senior author Zheng-Yi Chen, an associate professor at Harvard Medical School, expressed optimism about the study’s implications, stating, “This really opens the door to developing other treatments for different kinds of genetic deafness.”
The OTOF gene mutation targeted in the study is considered an attractive candidate for gene therapy due to its simplicity, involving a single mutation and causing no physical damage to cochlear cells. The study attracted significant interest, with 425 potential participants initially responding to the call for study partners. After screening, only six were enrolled, emphasizing the urgent need for effective treatments for congenital deafness lacking approved drugs.
Four of the participants had cochlear implants, allowing interpretation of speech and sound with training. The remaining two, aged one and two, had no implants and were completely deaf when the implants were switched off.
The researchers faced a unique challenge in delivering the gene into the cochlea, as the OTOF gene was too large for conventional viral vectors. They ingeniously overcame this obstacle by dividing the gene into two halves and using two different viruses to deliver them. This innovative approach allowed for the assembly of the complete protein within the target cells.
After a waiting period of four to six weeks, signs of hearing restoration began to emerge in five of the six participants. The older children, when tested without their cochlear implants, demonstrated an ability to understand and respond to speech, even in noisy environments. The youngest participants also showed improvements, though they were too young for certain tests.
While five participants showed significant progress, one did not exhibit improvement. Researchers speculate that an immune reaction to the viral vector may have been a contributing factor.
The success of this experimental gene therapy marks a promising step forward in the pursuit of effective treatments for genetic deafness, offering hope to countless individuals affected by congenital hearing impairments.
