"Our gene therapy protocol is not yet ready for clinical trials—we need to tweak it a bit more—but in the not-too-distant future we think it could be developed for therapeutic use in humans," says Jeffrey Holt, PhD, a scientist in the Department of Otolaryngology and F.M. Kirby Neurobiology Center at Boston Children's and an associate professor of Otolaryngology at Harvard Medical School...
To deliver the healthy gene, the team inserted it into an engineered virus called adeno-associated virus 1, or AAV1, together with a promoter—a genetic sequence that turns the gene on only in certain sensory cells of the inner ear known as hair cells. They then injected the gene-bearing AAV1 into the inner ear, with these findings:
- In the recessive deafness model, gene therapy with TMC1 restored the ability of sensory hair cells to respond to sound—producing a measurable electrical current—and also restored activity in the auditory portion of the brainstem.
- Most importantly, the deaf mice regained their ability to hear. To test hearing, the researchers placed the mice in a "startle box" and sounded abrupt, loud tones. "Mice with TMC1 mutations will just sit there, but with gene therapy, they jump as high as a normal mouse," says Holt. (The force of their jump was measured by a plate on the floor underneath them; it was detectable at sounds beginning around 80 decibels.)
- In the dominant deafness model, gene therapy with a related gene, TMC2, was successful at the cellular and brain level, and partially successful at restoring actual hearing in the startle test...(continued)