Researchers have successfully restored hearing in adult mice with inherited hearing loss using gene editing. By disabling a damaged copy of a gene called microRNA (miRNA), the mice were able to regain their hearing. This innovative approach shows promising potential for treating inherited hearing loss in humans in the future.
A team of researchers led by Zheng-Yi Chen, DPhil., from Mass Eye and Ear in Boston, focused on studying a rare genetic form of deafness known as autosomal dominant deafness-50 (DFNA50). This type of deafness is caused by mutations in the microRNA-96 (MIR96) gene. MiRNAs are genetic components that regulate gene activity, acting like a master switch. Mutations in miRNAs have been associated with various forms of inherited hearing loss. In individuals with DFNA50, progressive hearing loss typically begins during adolescence.
Previous studies had demonstrated the effectiveness of gene therapy and gene editing in treating genetic deafness in newborn mice. However, this research is the first to show successful gene editing in the inner ear of adult animals. The inner ear of a human is fully developed at birth, whereas a newborn mouse’s inner ear is still evolving both structurally and functionally.
The researchers targeted a specific mutation in the MIR96 gene, which affects genes crucial for the development and functioning of hair cells in the ear. These hair cells act as sensors for sound and motion and are essential for hearing.
The team utilized a CRISPR/Cas9 gene editing technique and delivered the gene editing components to the inner ear hair cells of mice with the MIR96 mutation using an adeno-associated virus (AAV). They tested the treatment on both newborn and adult mice with hearing loss, with better outcomes observed with early intervention.
According to Chen, gene editing is particularly effective for genetic deafness as a single mutation in one gene copy can disrupt the entire gene’s function, leading to disease. By targeting and correcting this mutation, the researchers were able to restore gene function effectively.
Chen emphasized the importance of creating a mouse model that mirrored the genetic mutation and progressive hearing loss seen in individuals with DFNA50.
The study showed sustained hearing restoration in the treated animals for at least nine months, suggesting the potential applicability of this approach in humans. Safety tests indicated that the delivery of the virus carrying the gene editing components did not integrate into the cell genome, reducing potential side effects.
This research marks a significant step forward in demonstrating the feasibility of gene editing in adult mice. Further preclinical tests in various animal models will be necessary before this treatment can advance to clinical trials.
The success of this approach opens up possibilities for treating other forms of genetic deafness caused by similar mutations in the MIR96 gene. The researchers have developed a method to target multiple MIR96 mutations, offering a promising avenue for addressing various types of hearing loss originating from different gene mutations.
Chen and his collaborators have also reported promising outcomes from clinical trials involving a gene therapy approach for another form of deafness, DFNB9.
Advancements in understanding and treating genetic hearing loss, coupled with the success of gene therapy and now genome editing, herald a new era of treatment options for individuals with genetic deafness.
The research team received partial funding from the NIH Common Fund’s Somatic Cell Genome Editing (SCGE) program, the National Institute on Deafness and other Communicative Disorders, and the National Human Genome Research Institute, showcasing the collaborative effort across various institutes to drive scientific breakthroughs in this field.
