Researchers Restore Hearing in Deaf Mice Using Gene Therapy Delivered Through Cerebrospinal Fluid
A groundbreaking study led by an international team of researchers has successfully restored hearing in mice using a new method of gene therapy. By delivering the therapy through cerebrospinal fluid via a little-understood passage into the inner ear, the scientists were able to repair inner ear hair cells and restore hearing in deaf mice.
The findings, published in the journal Science Translational Medicine, offer hope for the development of a similar therapy to restore hearing in humans.
Dr. Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester and the University of Copenhagen, explained the significance of the research, stating, “These findings demonstrate that cerebrospinal fluid transport comprises an accessible route for gene delivery to the adult inner ear and may represent an important step towards using gene therapy to restore hearing in humans.”
The study was a collaboration between researchers at the University of Rochester, the University of Copenhagen, and the Karolinska Institute in Stockholm, Sweden, led by Dr. Barbara Canlon.
The number of individuals worldwide with hearing loss is projected to reach 2.5 billion by the middle of the century. The primary cause of hearing loss is the death or loss of function of hair cells in the cochlea, which relay sounds to the brain. This can occur due to mutations of critical genes, aging, noise exposure, and other factors.
While hair cells are not naturally regenerated in humans and other mammals, gene therapies have shown promise in repairing these cells in neonatal and young mice. However, the challenge lies in delivering gene therapy to the cochlea without causing damage. As both mice and humans age, the cochlea becomes enclosed in the temporal bone, making surgical intervention risky.
In the current study, researchers discovered a little-known passage into the cochlea called the cochlear aqueduct. This thin bony channel, suspected of being involved in balancing pressure in the ear, also acts as a conduit between the cerebrospinal fluid in the inner ear and the rest of the brain.
Using advanced imaging and modeling technologies, the researchers mapped the flow of fluid through the cochlear aqueduct and into the inner ear. They then injected an adeno-associated virus into the cisterna magna, a reservoir of cerebrospinal fluid at the base of the skull. The virus traveled through the cochlear aqueduct and delivered a gene therapy that repaired the function of the hair cells, restoring hearing in adult deaf mice.
Dr. Nedergaard emphasized the potential impact of this new delivery method, stating, “This new delivery route into the ear may not only serve the advancement of auditory research but also prove useful when translated to humans with progressive genetic-mediated hearing loss.”
The study highlights the potential of utilizing the brain’s natural fluid flow and the glymphatic system for drug delivery to the auditory system, as well as other parts of the brain. The glymphatic system is the brain’s unique waste removal process, first described by the Nedergaard laboratory in 2012.
The research was supported by various foundations and institutions, including the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, and the European Union’s Horizon 2020 Research and Innovation Programme.
With the promising results of this study, the development of a gene therapy-based treatment for hearing loss in humans may be within reach. As research continues to advance, there is hope for the millions of individuals living with hearing impairment worldwide.