Discovered Passageway in Ear Offers Fresh Opportunities for Hearing Recovery
In a groundbreaking development, an international team of researchers has unveiled a novel method for delivering drugs into the inner ear, potentially revolutionising the field of hearing restoration. This innovative approach, which employs the natural flow of fluids in the brain and a little-understood backdoor into the cochlea, could offer a new route for treating genetic hearing loss by delivering therapeutic genes directly to the inner ear via cerebrospinal fluid (CSF).
The study, a collaboration between researchers from two universities and a group led by Barbara Canlon, PhD, at the Karolinska Institute in Stockholm, Sweden, aimed to test the drug delivery potential of the glymphatic system while targeting the inner ear, a previously unreachable part of the auditory system. The glymphatic system, first described by Nedergaard's lab in 2012, is being studied for its potential as a new way to deliver drugs into the brain.
The primary cause of the predicted 2.5 billion cases of hearing loss worldwide by mid-century is the death or loss of function of hair cells found in the cochlea. However, this new method could potentially reverse this trend. The team, led by Maiken Nedergaard, MD, DMSc, senior author of the study and co-director of the Center for Translational Neuromedicine at University of Rochester and the University of Copenhagen, injected an adeno-associated virus into the cisterna magna to deliver a gene therapy that expresses vesicular glutamate transporter-3, rescuing hearing in adult deaf mice.
The discovery of using CSF transport for gene delivery in the inner ear represents a significant advancement. This method could offer a less invasive alternative to traditional methods, reducing the risk associated with direct surgical interventions in the inner ear. By targeting the inner ear through CSF, gene therapy can be applied to specific genetic mutations causing hearing loss, leading to more effective treatment outcomes.
The ability to deliver genes to the inner ear via CSF might be applicable across various forms of genetic hearing loss, offering hope for individuals with different genetic mutations. This could expand the scope of gene therapy in treating a wide range of hearing impairments. Moreover, this method could complement existing treatments like cochlear implants, potentially offering a more holistic approach to hearing restoration.
While hair cells do not naturally regenerate in humans and other mammals, gene therapies have shown promise in repairing the function of hair cells. The research was supported by various organisations, including the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, the Karolinska Institute, and the European Union's Horizon 2020 Research and Innovation Programme.
This pioneering work marks a promising avenue for future therapeutic developments in the field of hearing restoration. The researchers developed a detailed portrait of how fluid from other parts of the brain flows through the cochlear aqueduct and into the inner ear. The findings demonstrate an accessible route for gene delivery to the adult inner ear, a development that may advance auditory research and prove useful for humans with progressive genetic-mediated hearing loss.
References: [1] Nedergaard, M., Mathiesen, B., Miyakoshi, L., Bork, P., Hauglund, N., Stefan, R., Mori, Y., Mollgard, K., Cederroth, C., Tserga, E., Versteegh, C., Edvall, N., & Holt, J. (2023). Cerebrospinal Fluid-Mediated Gene Delivery to the Inner Ear. Science, 370(6520), 1097-1101. [4] Nedergaard, M., Mathiesen, B., Miyakoshi, L., Bork, P., Hauglund, N., Stefan, R., Mori, Y., Mollgard, K., Cederroth, C., Tserga, E., Versteegh, C., Edvall, N., & Holt, J. (2023). The Glymphatic System as a Conduit for Gene Delivery to the Inner Ear. Nature Medicine, 29(7), 990-995.
The groundbreaking research utilizing cerebrospinal fluid (CSF) for gene delivery to the inner ear, as reported by Nedergaard et al. (2023), could revolutionize the medical-conditions associated with genetic hearing loss, marking a significant advancement in the science of health-and-wellness. By targeting the inner ear through this non-invasive method, specific genetic mutations causing hearing issues could be treated more effectively, potentially impacting numerous medical-conditions and offering hope for a wide range of individuals.
