In a groundbreaking achievement, a team of international researchers has unveiled an innovative method for administering gene therapy to restore hearing. This pioneering discovery harnesses the natural flow of cerebrospinal fluid within the brain, utilizing a previously obscure entryway into the cochlea. By implementing this technique to deliver gene therapy aimed at rejuvenating inner ear hair cells, the scientists have achieved a remarkable feat: the restoration of hearing in deaf mice.
The study, spearheaded by Maiken Nedergaard, MD, DMSc, and senior author of the research published in Science Translational Medicine, highlights the potential of cerebrospinal fluid transport as a viable route for gene therapy in the adult inner ear. This development represents a significant stride towards employing gene therapy to address hearing loss in humans.
Collaborating across borders, this scientific endeavor enlisted the expertise of researchers from the University of Rochester, the University of Copenhagen, and the Karolinska Institute in Stockholm, Sweden, led by Barbara Canlon, Ph.D., in the Laboratory of Experimental Audiology.
The global prevalence of mild to complete hearing impairment is projected to surge to approximately 2.5 billion individuals by the middle of this century. The principal cause of this widespread auditory challenge lies in the degeneration or dysfunction of cochlear hair cells, responsible for transmitting auditory signals to the brain. This impairment can arise from a variety of factors, including genetic mutations, the aging process, exposure to excessive noise, and other contributing elements.
Notably, hair cells do not naturally regenerate in humans and other mammals. Nevertheless, gene therapies have exhibited promise in rejuvenating hair cell function in neonatal and very young mice in previous studies. However, as both mice and humans age, the cochlea, an already delicate structure, becomes encased within the temporal bone. Consequently, any surgical attempts to access the cochlea and administer gene therapy risk causing damage to this sensitive region, potentially altering one’s hearing abilities.
The study sheds light on a previously obscure conduit into the cochlea known as the cochlear aqueduct. Despite its name conjuring images of grand architectural features, this channel is a slender bony passage no wider than a single strand of hair. Traditionally associated with maintaining ear pressure equilibrium, the cochlear aqueduct has now been revealed to serve as a conduit connecting the cerebrospinal fluid within the inner ear to the broader brain network.
Researchers are gaining a deeper understanding of the glymphatic system’s mechanics, a unique brain waste removal process initially elucidated by the Nedergaard lab in 2012. Given that the glymphatic system propels cerebrospinal fluid deep into brain tissues to cleanse toxic proteins, scientists have contemplated its potential as a groundbreaking approach for drug delivery into the brain—a formidable challenge in the realm of neurological disorder treatment.
Furthermore, recent discoveries indicate that the intricate fluid dynamics orchestrated by the glymphatic system extend to the peripheral nervous system, including the eyes and the auditory system. This study presented an opportunity to assess the drug delivery potential of the glymphatic system while targeting an erstwhile inaccessible facet of the auditory system.
Leveraging advanced imaging and modeling technologies, the research team meticulously elucidated the pathway through which fluids from different brain regions traverse the cochlear aqueduct and reach the inner ear. Subsequently, they administered an adeno-associated virus into the cisterna magna, a substantial reservoir of cerebrospinal fluid located at the base of the skull. This virus navigated its way through the cochlear aqueduct, delivering a gene therapy that expresses vesicular glutamate transporter-3, a protein crucial for enabling hair cells to transmit signals. As a result, hearing was restored in adult mice previously afflicted with deafness.
“This novel avenue for ear-targeted drug delivery holds the potential not only to advance auditory research but also to offer a promising avenue for addressing progressive genetic-related hearing loss in humans,” affirmed Nedergaard.
This remarkable research was made possible through the collaboration of a diverse team of experts, including Barbara Mathiesen, Leo Miyakoshi, Peter Bork, Natalie Hauglund, Ryszard Stefan, Yuki Mori, and Kjeld Mollgard from the University of Copenhagen; Christopher Cederroth, Evangelia Tserga, Corstiaen Versteegh, Niklas Edvall, and Barbara Canlon from the Karolinska Institute; and Jeffrey Holt from Harvard University. Funding for this research was generously provided by various organizations, including the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, the Knut and Alice Wallenberg Foundation, the Karolinska Institute, and several others committed to advancing the frontiers of auditory science.
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Frequently Asked Questions (FAQs) about Hearing Restoration via Cerebrospinal Fluid
What is the key discovery presented in this research?
The research unveils a groundbreaking method for restoring hearing by delivering gene therapy through cerebrospinal fluid. This innovative approach repairs inner ear hair cells, offering hope for addressing hearing loss in humans.
Why is this discovery significant?
This discovery is significant because it provides a potential solution for the growing global issue of hearing loss, with an estimated 2.5 billion individuals expected to experience some degree of hearing impairment by mid-century. It addresses the root cause of hearing loss by rejuvenating the function of inner ear hair cells.
How does the gene therapy work?
The gene therapy is administered via an adeno-associated virus, which expresses a crucial protein called vesicular glutamate transporter-3. This protein enables the damaged hair cells in the inner ear to transmit signals, ultimately restoring hearing in the test subjects, which were deaf mice in this study.
What is the role of the cochlear aqueduct in this research?
The cochlear aqueduct, despite its small size, plays a vital role in this research. It serves as a conduit between the cerebrospinal fluid found in the inner ear and the broader brain network. This pathway allows the adeno-associated virus carrying the gene therapy to reach the inner ear, where it can repair the hair cells responsible for hearing.
What are the implications of this study for human hearing loss?
This research holds significant promise for addressing genetic-mediated hearing loss in humans. By demonstrating the feasibility of delivering gene therapy via cerebrospinal fluid to rejuvenate inner ear hair cells, it paves the way for potential treatments to restore hearing in individuals facing this condition.
Who were the key contributors to this research?
The research was conducted by an international team of experts, including researchers from the University of Rochester, the University of Copenhagen, and the Karolinska Institute in Stockholm, Sweden. Maiken Nedergaard, MD, DMSc, and Barbara Canlon, Ph.D., were among the senior authors leading this collaborative effort.
What organizations supported this research?
Funding for this groundbreaking research was generously provided by several organizations, including the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, the Knut and Alice Wallenberg Foundation, the Karolinska Institute, and others committed to advancing auditory science.
1 comment
this cud b a game changer 4 ppl with hearin loss, truly amazin’ reesearch.