Promising new work from researchers at Harvard may lead to a one-time treatment possibility for certain kinds of hearing loss. Genetics influences about half of all hearing loss, for which treatment options are limited. Drs. Liu and Chen led a research team and showed recently that a molecular technique can restore hearing in mice with a certain from of genetic hearing loss.
Mutations in at least 100 alleles (versions) of genes impact hearing ability in humans and about 1 in 5 of these alleles are dominant. This means that if one parent has one of these bad alleles and a child inherits it, the mutation will express, even if the other parent has normal alleles. In this study, the researchers targeted the Tmc1 gene, which holds the code to make Tmc1 protein. Sensory cells in the inner ear need this gene to make this protein. There is a dominant, mutant allele for the gene that differs from the normal allele by only one nucleotide. This mutation prevents the protein (and the cell) from functioning properly. A certain strain of mice called Tmc1 Beethoven has a mutation identical to the one in humans. The mutation causes deafness in both humans and mice.
This research team targeted this specific mutation in the mouse model and repaired it. They used a genome-editing tool known as Cas9. This mechanism has a nucleotide sequence, which acts as a key that searches for a lock—normally, foreign material from a virus. If the lock and key match, then Cas9 acts like scissors to cut out the foreign material. The researchers engineered this tool for their own purpose by changing the key so that it would instead match the bad Tmc1 allele, find it, and then cut it out. After cutting the mutant allele, the normal recessive allele expresses and restores hearing function.
This mechanism is not an exact tool. Sometimes the key will match the wrong lock if it is similar enough to the target DNA. After checking areas where this was likely to occur, the researchers confirmed that there was some minor unintended cutting, but not in areas involved in hearing. In conclusion, this novel method was 25% effective in adult mice. However promising, potential treatment for humans is not in the immediate future.