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Gene therapy trial for OTOF-related deafness shows hearing recovery in 90% of participants over 2.5 years

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Gene Therapy Shows Promise in Treating Inherited Deafness

A recent single-arm, multicenter trial has demonstrated promising results for a gene therapy targeting a specific form of congenital deafness. The trial involved 42 participants, aged from 0.8 to 32.3 years, across eight centers.

Hearing was recovered in 90% of participants treated with the investigational gene therapy.

Trial Design and Safety

Participants received an adeno-associated virus (serotype 1) carrying a human OTOF coding transgene (AAV1-hOTOF). They were divided into three vector dose groups and followed for up to 2.5 years.

No dose-limiting toxicities were observed within the critical first 6 weeks after treatment. The most notable adverse event was a Grade 3 decrease in neutrophil count.

Hearing Recovery Results

The therapy aimed to treat autosomal recessive deafness 9, caused by mutations in the OTOF gene, which typically results in severe-to-complete congenital hearing loss.

Auditory brainstem response thresholds showed marked and sustained improvement:

  • Baseline: Greater than 97 ± 1 dB
  • 1 Year: 54 ± 3 dB
  • 1.5 Years: 51 ± 3 dB
  • 2 Years: 50 ± 3 dB
  • 2.5 Years: 42 ± 5 dB

Behavioral audiometry results corroborated this recovery, improving from greater than 96 ± 3 dB at baseline to 37 ± 5 dB at the 2.5-year mark.

Factors Influencing Outcomes

The study revealed several factors associated with the degree of hearing improvement:

  • Age: Participants between 0.5 and 18 years of age showed greater hearing improvement than adult participants.
  • Baseline Status: A higher number of present distortion product otoacoustic emissions at baseline was linked to better recovery.
  • Genetic Variant: Having biallelic non-truncated OTOF variants was also associated with more favorable outcomes.

Furthermore, participants who recovered hearing demonstrated a gradual improvement in speech perception over time.

Context and Significance

This trial builds on earlier, smaller studies that hinted at the benefits of gene therapy for this condition. The new data help clarify the safety and efficacy of the treatment across a broader age range and over a longer follow-up period.

The trial is registered in the Chinese Clinical Trial Registry under identifier ChiCTR2200063181.