An unexpected doorway to the ear opens new possibilities for hearing recovery — ScienceDaily

“These findings indicate that cerebrospinal fluid transport constitutes a viable pathway for gene delivery to the inner ear in adults, and may be useful for using gene therapy to restore hearing in humans.” It could be an important step forward in the future,” said senior author Miken Nedergaard, MD, DMSc, a senior author on the new paper.Research published in journals scientific translational medicine.

Nedergaard is co-director of the Translational Neuromedicine Center at the University of Rochester and the University of Copenhagen. The research is the result of a collaboration between researchers from both universities and a group led by Dr. Barbara Canron. In the Experimental Audiology Laboratory at the Karolinska Institutet in Stockholm, Sweden.

The number of people worldwide who are expected to suffer from mild to complete hearing loss is expected to increase to approximately 2.5 billion by mid-century. The main cause is the death or loss of function of hair cells in the cochlea (which carry sound to the brain) due to factors such as mutations in key genes, aging, and exposure to noise.

Although hair cells do not regenerate naturally in humans and other mammals, gene therapy has shown promise, and another study restored hair cell function in neonatal and very young mice. have succeeded in However, as both mice and humans age, the cochlea, which is originally a delicate structure, becomes surrounded by the temporal bone. At present, attempts to reach the cochlea and perform surgical gene therapy risk damaging this sensitive area and altering hearing.

In a new study, researchers describe a little-understood passageway into the cochlea called the cochlear aqueduct. Although its name evokes images of monumental stone structures, the cochlear aqueduct is a thin, bony tube no larger than a hair. Though thought to play a role in balancing pressure within the ear, new research suggests that the cochlear water duct also functions as a conduit between the cerebrospinal fluid in the inner ear and the rest of the brain. was shown.

Scientists are developing a clearer picture of how the brain’s unique waste removal process, the glymphatic system, first described by the Nedergaard lab in 2012, works. Researchers have noted that the glymphatic system pumps cerebrospinal fluid deep into brain tissue to wash away toxic proteins. This could be a new way to deliver drugs to the brain, a major challenge in drug development for neurological diseases.

The researchers also found that the complex fluid movements caused by the glymphatic system extend to the peripheral nervous system, including the eyes and ears. This new study offers an opportunity to test the drug-delivery potential of the glymphatic system and to target previously unreachable parts of the auditory system.

Using a number of imagination and modeling techniques, the researchers were able to develop a detailed depiction of how fluid from other parts of the brain flows through the cochlear aqueduct into the inner ear. . The team then injected the adeno-associated virus into the cisterna magna, a large reservoir of cerebrospinal fluid, at the base of the skull. The virus enters the inner ear via the cochlear aqueduct and is treated with gene therapy to express a protein called vesicular glutamate transporter-3, which enables hair cells to transmit signals. Restored hearing.

“This new route of delivery to the ear may not only help advance hearing research, but may also prove useful when applied to humans with progressive hereditary hearing loss.” Yes,” said Nedergaard.

Other co-authors on the study include Barbara Matthiessen, Leo Miyakoshi, Peter Volk, Natalie Hauglund, Lizard Stefan, Yuki Mori, and Keld Morgard of the University of Copenhagen. Christopher Sederos, Evangelia Tzerga, Korstian Versteg, Niklas Edvard, and Barbara Canron of the Karolinska Institutet. And Jeffrey Holt of Harvard University. This study was funded by the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, the Knut and Alice Wallenberg Foundation, the Karolinska Institutet, the Tista Skoran Foundation, Hervorskningsvonden, and the European Union’s Horizon 2020. Research and Innovation Program, Danish Neuroscience Society, US Army Research Service, Human Frontier Science Program, Miriam and Sheldon G. Adelson PhD Medical Research Foundation, Simmons Foundation, Jeff & Kimberly Barber Foundation, and Poole Audition Foundation.