A team of researchers at Mass Eye and Ear successfully restored hearing in adult mouse models with inherited deafness caused by mutations in microRNA using a novel in vivo CRISPR genome editing approach. This breakthrough paves the way for potential applications in humans with similar genetic deafness in the future.
In their study, the researchers investigated the safety and effectiveness of an AAV-mediated genome editing approach and found it to have a good safety profile, minimal off-target effects, and no long-term integration of the AAV vector in the genome. This implies low potential risk and supports the feasibility of future clinical applications in humans.
The study, led by Dr. Zheng-Yi Chen and his team at Mass Eye and Ear, was published in Science Translational Medicine on July 10.
This research opens up possibilities for developing treatments for various forms of genetic hearing loss. Dr. Chen, who holds the Ines and Fredrick Yeatts Chair in Otolaryngology at Mass Eye and Ear and is an associate professor at Harvard Medical School, believes that genome editing interventions could potentially stop or reverse hearing loss progression in affected individuals, including adults.
About one in 500 newborns experience genetic hearing loss, with no approved therapeutics currently available for treatment.
The researchers focused on a specific mutation in the microRNA-96 (MiR-96) gene, implicated in progressive hearing loss in mice and humans. This mutation is linked to DFNA50, a form of dominant inherited progressive hearing loss. By targeting and disrupting this mutation using a CRISPR/Cas9 genome editing approach delivered via an adeno-associated virus (AAV), the team preserved auditory function in mouse models with progressive hearing loss.
CRISPR/Cas9 delivery during early development and in adult stages showed long-term preservation of auditory function, with earlier intervention being more effective.
Dr. Chen and his team are collaborating with Mass General Brigham’s Gene and Cell Therapy Institute to conduct further preclinical studies to advance this treatment approach towards human clinical trials. This research showcases the potential of gene therapy in treating hearing loss and underscores the commitment to translating scientific breakthroughs into transformative treatments.
This groundbreaking study offers hope for future clinical trials targeting genetic hearing impairments, including the restoration of auditory function in individuals with genetic forms of hearing loss. Dr. Chen’s team is also exploring gene therapy approaches for DFNB9 deafness caused by mutations in the OTOF gene, showcasing positive results in clinical trials in China.
Dr. Chen envisions leveraging technology developed in previous trials, such as minimally invasive AAV delivery, to accelerate the development of editing therapy for hearing disorders.
With over 150 forms of genetic deafness, the research presents a promising avenue for patients who lacked effective treatment options beyond cochlear implants. Dr. Chen emphasizes the need for rigorous studies to build on these promising results to develop diverse treatment approaches for targeting various genetic mutations.
