Regeneron: DB-OTO Gene Therapy Restores Genetic Hearing Loss

1. DB-OTO gene therapy has been shown to improve auditory response in children with congenital hearing loss
2. DB-OTO is a promising alternative to cochlear implants to treat sensorineural hearing loss

The Latest

The open-label global phase 1/2 CHORD trial conducted by Decibel Therapeutics in partnership with Regeneron Genetic Medicines demonstrates the safety and efficacy of its gene therapy DB-OTO in two children born with profound hearing loss due to mutations in a single gene, otoferlin, which turns off auditory circuits. Regeneron has been staggering patient enrolment to monitor for safety observations before enrolling approximately 22 children with otoferlin-mutation hearing loss aged 17 years and younger. So far, the trial has demonstrated improved hearing back to normal levels with an average 80-decibel improvement from baseline in one child at 24 weeks. The second participant showed a 16-decibel improvement compared to the baseline at six weeks. The surgery and gene therapy were both well-tolerated with no treatment-related adverse events or serious adverse events.

Physician’s Perspective

Congenital hearing loss is a significant unmet medical need with no approved pharmacologic treatment options that affects approximately 1.7 out of every 1,000 children born in the U.S. Currently the standard of care is treatment with cochlear implants which skip transmission of sound through the ear, directly stimulating the auditory nerve and sending messages to the brain. However, gene therapies like DB-OTO could restore hearing more naturally. By transducing sound through the ear, patients can develop a more natural-sounding voice when compared with cochlear implants because of better auditory feedback. DB-OTO is a proof of concept showing that genetic hearing loss can be treated with gene therapy.

Molecular Targets

DB-OTO is an adeno-associated viral vector that delivers gene therapy via intracochlear injection under general anesthesia to provide a payload of cDNA that expresses functional otoferlin protein in hair cells. Otoferlin protein is expressed in the sensory hair cells of the ear, which have tiny cilia that move as vibrations come into the ear. These cells help signal between the auditory nerve and hair cells, passing information from the ear to the brain. Children with otoferlin genetic hearing loss have hair cells that can detect signals but can’t send messages from the ear to the brain. However, with the introduction of otoferlin cDNA, hair cells can produce the protein long-term, thus restoring auditory function.

Company History

Regeneron is an American biotechnology company headquartered in Westchester County, New York. The company has helped design drugs that have transformed the lives of patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular diseases, metabolic diseases, hematologic conditions, infectious diseases, and other rare diseases.

Further Reading: https://investor.regeneron.com/news-releases/news-release-details/latest-db-oto-results-show-dramatically-improved-hearing-normal

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