Research teams at Harvard Medical School and Boston Children’s Hospital are using an innovative approach to the problem of genetic hearing loss. This new research uses a gene-editing method to salvage the hearing of mice with hereditary hearing loss. In a process that targets a bad copy of a gene while sparing the good gene, the research team is seeing tremendous results from the therapy. Furthermore, this process is succeeding without off-target effects resulting from the treatment. This news is exciting as it may open the door for the treatment of human diseases that result from single-point mutations.
This system successfully identifies a single misspelled letter in the defective copy of a gene for hearing, disables the bad replication while sparing the healthy one. Hopefully, it will find use with other dominantly inherited diseases. The mice named Beethoven mice, underwent treatment for a genetic mutation that is responsible for progressive hearing loss in humans. This type of hearing loss often results in profound deafness by the time an individual is in their mid-20s. The gene therapy uses a scientifically engineered adenovirus to deliver a copy of the Tmc1 gene into the ear, causing the Beethoven mice to go deaf by six months of age.
The team visualized the hearing cells of the Beethoven mice with an electron microscope. The researchers were able to see a gradual loss of hearing cells in the untreated mice as well as deterioration of the structure. The treated Beethoven mice and the treated healthy mice both retained a normal count of hearing cells with fully intact or near intact structure. The scientists tested the treatment in human cells that were carrying the Beethoven mutation. Just like the mice, DNA analysis indicates that editing occurred in the mutant copy of the gene while sparing the normal one.
The researchers tested the auditory brainstem response of the mice, which shows how much sound is perceived by hair cells in the inner ear. Two months after the start of the gene-editing therapy, the treated Beethoven mice’s hearing was much better than the non-treated mice. The treated mice were able to receive sounds the equivalent of normal speech. A group of the treated mice still maintain normal hearing one year after the initial process. It is also notable that mice without the gene defect did not experience hearing loss as a result of the gene therapy. This fact further demonstrates that the treatment selectively targets the aberrant copy of the gene.
Due to its ability to target single-point genetic mutations, the research team feels like the CRISPR/Cas9 approach holds much promise for other forms of inherited deafness resulting from single-point mutation. The researchers believe that the treatment can selectively silence genes that carry single-point mutations as well as a treatment for other types of human disease. The gene-editing approach is the first step in a process with tremendous potential.