Using gene therapy, researchers at Boston Children's Hospital and Harvard Medical School have restored hearing in mice with a genetic form of deafness. Their work, published online July 8 by the journal Science Translational Medicine, could pave the way for gene therapy in people with hearing loss caused by genetic mutations. "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.

More than 70 different genes are known to cause deafness when mutated. Holt, with first author Charles Askew and colleagues at École Polytechnique Fédérale de Lausanne in Switzerland, focused on a gene called TMC1. They chose TMC1 because it is a common cause of genetic deafness, accounting for 4 to 8 percent of cases, and encodes a protein that plays a central role in hearing, helping convert sound into electrical signals that travel to the brain.

The researchers tested gene therapy in two types of mutant mice. One type had the TMC1 gene completely deleted, and is a good model for recessive TMC1 mutations in humans: Children with two mutant copies of TMC1 have profound hearing loss from a very young age, usually by around 2 years. 

The other type of mouse, called Beethoven, has a specific TMC1 mutation--a change in a single amino acid--and is a good model for the dominant form of TMC1-related deafness. In this form, less common than the recessive form, a single copy of the mutation causes children to gradually go deaf beginning around the age of 10 to 15 years.