Lancet

Gene therapy enables 11-year-old boy to hear for the first time

January 30, 2024

On January 23, 2024, the Children's Hospital of Philadelphia (CHOP) announced that the hearing of an 11-year-old boy, who was born with hereditary deafness, had improved enough following a gene therapy procedure that he now has only mild to moderate hearing loss in the treated ear.

The boy, who was born profoundly deaf in both ears, was the first patient to receive this gene therapy as part of the AK-OTOF-101 clinical trial.

According to trial results published in Lancet, AAV1-hOTOF gene therapy was found to be safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterized by congenital or prelingual, severe-to-complete, bilateral hearing loss. No pharmacological treatment is currently available for congenital deafness. 

• This single-arm, single-center trial enrolled children (ages 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants.
• A single injection of AAV1-hOTOF was administered into the cochlea through the round window.
• Primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools.
• Between Oct 19, 2022 and June 9, 2023, researchers screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 10^11 vector genomes [vg] and five received 1.5 × 10^12 vg).
• All participants completed follow-up visits up to week 26.
• No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant).
• Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0.5-4.0 kHz.
• In the participant who received the 9 × 10^11 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks.
• In those who received 1.5 × 10^12 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks.
• Speech perception was improved in participants who had hearing recovery.

Sources:

LV J, et al. (2024, January 24). Lancet. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. https://pubmed.ncbi.nlm.nih.gov/38280389/

(2024, January 23). PR Newswire. Children's Hospital of Philadelphia. Children's Hospital of Philadelphia Performs First in U.S. Gene Therapy Procedure to Treat Genetic Hearing Loss. https://www.prnewswire.com/news-releases/childrens-hospital-of-philadelphia-performs-first-in-us-gene-therapy-procedure-to-treat-genetic-hearing-loss-302042233.html