In a groundbreaking development, a gene therapy approach has successfully restored hearing in five children who were born deaf. This innovative method, overcoming a significant obstacle posed by large genes, holds promise for potential application in treating various other conditions, as indicated by researchers.
The research, carried out in Fudan, China, under the joint leadership of Zheng-Yi Chen from the Massachusetts Eye and Ear Infirmary and Harvard Medical School, along with collaborators from Fudan University’s Eye & ENT Hospital, focused on six children aged 1 to 7 afflicted with an inherited mutation of the OTOF gene. This gene produces a vital protein essential in transmitting signals from the ear to the brain.
Five of the six children displayed notable improvements in hearing throughout the 26-week trial, with researchers describing four outcomes as “robust.” Given the critical role of hearing in language acquisition, the study also assessed speech perception, revealing enhanced abilities in all five responsive participants.
The significance of this achievement resonates in the words of Zheng-Yi Chen, who emphasized the broader implications: “This opens the door to developing other treatments for different kinds of genetic deafness.” Furthermore, Chen underscored the translational aspect of the study, affirming its validity in human applications based on prior laboratory animal research.
The condition targeted in this study, DFNB9, stems from a mutation in the OTOF gene, resulting in total deafness. The gene encodes the otoferlin protein crucial for transmitting auditory signals. Notably, this genetic anomaly presented an attractive target for gene therapy due to its relative simplicity, involving a single mutation without physical damage to cochlear cells.
Before commencing the trial, researchers encountered a significant technical hurdle related to the size of the OTOF gene. This challenge was addressed by dividing the gene into two segments, encapsulating them into separate viruses, and delivering the mixture into the cochlea. Despite inserting the gene halves at different sites within cells’ DNA, the cellular machinery successfully assembled the complete protein, restoring signal transmission to the brain.
The trial results demonstrated progressive hearing improvement for five out of the six participants, particularly notable in the older children who could understand and respond to speech within 26 weeks. Notably, anecdotal evidence highlighted early signs of responsiveness in some participants even before formal testing.
Reflecting on the emotional impact, Yilai Shu, a study’s senior author, recounted parents’ reactions upon witnessing their children’s newfound ability to hear. The project, conducted in December 2022, marked a significant milestone as the first instance of gene therapy to address this condition.
The researchers plan to monitor the participants’ progress and initiate studies involving a more diverse demographic. Pending successful outcomes, approval of this treatment by U.S. federal regulators could be achieved within three to five years, offering hope for a transformative intervention in genetic deafness treatment.