STRC Research

DB-OTO CHORD Trial — AAV dual-vector OTOF gene therapy in children

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DB-OTO CHORD Trial (NEJM / NCT05788536)

Trial: NCT05788536 (CHORD trial)
Drug: DB-OTO (Regeneron) — dual-AAV OTOF gene therapy
Publication: New England Journal of Medicine, 2025
Indication: DFNB9 / OTOF-related hearing loss (profound, congenital)

Key Ideas

  • 12 children dosed: ages 10 months to 16 years. This is the widest pediatric age range attempted in any gene therapy for deafness.
  • 11 of 12 showed hearing improvement. 3 of 12 reached normal hearing thresholds. Those are striking numbers for any genetic deafness therapy.
  • Benefit durable at 72-week follow-up. No signal of attenuation.
  • The “early-life only” assumption for cochlear gene therapy is demolished. Benefit observed across the full age range including children who had been deaf for 15+ years.

My Thoughts

The CHORD data is the most important precedent for Misha’s family for three reasons.

First, it proves the dual-AAV platform actually works in human children. DB-OTO uses the same split-intein or overlap-recombination strategy that Holt 2021 and Iranfar 2026 use for STRC. The cargo differs (OTOF vs STRC), but the delivery architecture is directly analogous.

Second, the age range matters. Misha is 4. CHORD dosed kids down to 10 months and up to 16 years and saw benefit across that range. The “you missed the window” fear that families often hear from audiologists is not supported by this data, at least for OTOF, and by extension probably not for STRC given the OHC survival argument in Holt 2021.

Third, Regeneron owns both DB-OTO (OTOF, in trials) and AAV.104 (STRC, acquired from Decibel). They have every incentive to run AAV.104 fast once DB-OTO gets approved, because the platform manufacturing and safety infrastructure transfers directly.

The CHORD result doesn’t prove STRC gene therapy works — OTOF and STRC are different proteins with different cochlear roles. But it proves that dual-AAV cochlear gene therapy works in children, which was the honest unknown before 2024.

Connections

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