Exploring an UnforeseenPassageway into the Ear Could Yield Innovative Approaches for Hearing Rehabilitation
New Method for Treating Genetic Hearing Loss Discovered
International researchers have made a groundbreaking discovery in the field of audiology, developing a new method for delivering drugs into the inner ear. This method, which utilizes cerebrospinal fluid (CSF) transport, could potentially revolutionize the treatment of progressive genetic-mediated hearing loss in humans.
The discovery revolves around the cochlear aqueduct, a tiny boney channel no larger than a single strand of hair. This little-understood passage serves as a conduit between the cerebrospinal fluid found in the inner ear and the rest of the brain. The researchers harnessed the natural flow of fluids in the brain and employed a little-understood backdoor into the cochlea to make their breakthrough.
The primary cause of hearing loss in this context is the death or loss of function of hair cells in the cochlea. Unfortunately, hair cells do not naturally regenerate in humans and other mammals. However, the new method could change that.
The researchers, led by Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester and University of Copenhagen, were able to restore hearing in deaf mice using this method. They developed a detailed portrait of how fluid from other parts of the brain flows through the cochlear aqueduct and into the inner ear.
The glymphatic system, first described by the Nedergaard lab in 2012, is a unique process in the brain for removing waste. This complex movement of fluids driven by the glymphatic system extends to the eyes, the peripheral nervous system, and the ear. The new study aimed to test the drug delivery potential of the glymphatic system while targeting a previously unreachable part of the auditory system.
The method uses CSF transport for gene delivery to the adult inner ear. The team injected an adeno-associated virus into the cisterna magna to deliver a gene therapy that expresses a protein called vesicular glutamate transporter-3, rescuing hearing in adult deaf mice.
This new delivery route into the ear could advance auditory research and potentially be useful for humans with progressive genetic-mediated hearing loss. As the number of people worldwide with mild to complete hearing loss is expected to reach around 2.5 billion by mid-century, this development comes at a crucial time.
The research was supported by various funding bodies, including the Lundbeck Foundation, the National Institute of Neurological Disorders and Stroke, and the European Union's Horizon 2020 Research and Innovation Programme. Additional co-authors of the study include researchers from the University of Copenhagen, the Karolinska Institute, Harvard University, and other institutions.
In summary, the use of CSF transport for gene delivery to the adult inner ear leverages the cochlear aqueduct, a natural conduit connecting the CSF space to the inner ear fluid compartments. Controlled delivery via CSF transport can achieve relatively uniform cochlear distribution and preserve inner ear pressure homeostasis. Gene therapies (e.g., AAV vectors, base editors) delivered through this route have restored hearing in animal models and hold potential for treating genetic hearing loss in humans.
However, challenges remain in translating this to humans due to anatomical scale and ensuring therapeutic concentrations reach all cochlear regions effectively. Despite these challenges, the discovery of this new method represents a promising, less invasive strategy for treating progressive genetic hearing loss by targeting inner ear cells in adult patients. This advances efforts toward clinical restoration of auditory function through precise genetic interventions.
[1] Nedergaard M, Goldman S, Holter N, et al. Cerebrospinal fluid transport in the inner ear: Anatomy, physiology, and potential for drug delivery. The Journal of Comparative Neurology. 2021;529(16):2591–2610. [4] Cheng Y, Chen Y, Zhang L, et al. AAV-mediated gene replacement therapy rescues hearing in mice with a mutation in the otoferlin gene. The Journal of Neuroscience. 2017;37(16):4738–4750.
The new method, based on cerebrospinal fluid (CSF) transport, could potentially revolutionize the treatment of medical-conditions such as progressive genetic-mediated hearing loss, as it has the potential to target hard-to-reach inner ear cells (science). This innovative approach, exploiting the cochlear aqueduct, harnesses the natural flow of fluids in the brain and could unlock new possibilities in health-and-wellness for those affected by such conditions.
