Imagine a world where children born deaf can hear for the first time. This once far-fetched dream is becoming a reality thanks to a recent breakthrough in genomic therapy. A new study published in Nature Medicine reports promising results from an innovative gene therapy designed to treat autosomal recessive deafness 9 (DFNB9).
DFNB9 is a genetic condition that leads to severe-to-complete hearing loss from birth or early childhood. It's caused by mutations in the OTOF gene, which encodes a crucial protein called otoferlin necessary for hearing. Without functional otoferlin, sound signals cannot be properly transmitted to the brain, resulting in deafness.
Researchers have been exploring gene therapy as a way to treat genetic disorders like DFNB9. In this approach, a healthy copy of the defective gene is delivered to the patient's cells using a viral vector. In previous studies, a single injection of an adeno-associated virus (AAV) carrying the human OTOF gene showed safety and some hearing improvement in one ear.
Building on this success, the researchers expanded their trial to test the therapy in both ears (binaural therapy) in children with DFNB9. Their latest paper presents interim results from this ongoing study.
Five children with DFNB9 who never received cochlear implants participated in the trial. Each received the gene therapy in both ears. The primary goals were to evaluate safety and to observe any improvements in hearing. Here’s what they found:
Safety: No serious adverse events or dose-limiting toxicities were reported. Out of 36 minor adverse events, the most common were increased lymphocyte counts and cholesterol levels, both manageable.
Efficacy: Remarkably, all five children showed significant improvement in hearing. Before therapy, their average auditory brainstem response thresholds were greater than 95 dB, indicating profound hearing loss. After therapy, these thresholds improved dramatically. For example:
Patient 1: Improved to 58 dB and 63 dB in the right and left ears, respectively.
Patient 2: Improved to 75 dB and 85 dB.
Patients 3, 4, and 5 showed similar improvements.
Beyond these quantitative measures, qualitative improvements were equally striking. All five children gained the ability to perceive speech and locate sounds. Here are some inspiring individual stories:
Patient 1: An 11-year-old girl, deaf since birth, began responding to her name and recognizing sounds within weeks. By 13 weeks, she could speak simple syllables like "ba" (father) and "ma" (mother).
Patient 2: This child, who couldn’t hear at all initially, could turn to his grandparents' calls within six weeks and started saying words like "ayi" (aunt) and "bai" (bye) by 26 weeks.
Patient 3: Similarly, this patient began responding to his name within three weeks and could dance to music and say words like "baba" (father) and "yeye" (grandfather) by 26 weeks.
This study offers a glimmer of hope for the 430 million people worldwide who suffer from disabling hearing loss, including 34 million children. Approximately 26 million people have congenital hearing loss, with 60% of these cases due to genetic factors like DFNB9.
While these interim results are promising, the trial is ongoing, and longer follow-up is needed to confirm the therapy's long-term safety and efficacy. If successful, this gene therapy could revolutionize the treatment of genetic hearing loss, offering a new lease on life for countless individuals.
For more details, you can check the trial registration at the Chinese Clinical Trial Registry: ChiCTR2200063181.
REFERENCE
Wang, H., Chen, Y., Lv, J. et al. Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results. Nat Med (2024). https://doi.org/10.1038/s41591-024-03023-5
