Method for using cerebrospinal fluid to deliver gene therapeutics to the inner ear and rescue hearing


An estimated 2.45 billion of individuals are predicted to have mild-to-complete hearing impairment by 2050. Current ameliorating therapy using hearing aids or cochlear implants remain insufficient in restoring the full capacities of auditory function. Gene therapy has shown promising results in animal models but the delivery of genetic material remains challenging and current methods are invasive surgeries that can cause damage to inner ear structures. Therefore, there is an unmet need to develop more efficient and less invasive methods to deliver gene therapies to the inner ear.

Technology Overview

Cerebrospinal fluid (CSF) transport by the glymphatic system is emerging as a new approach for brain-wide gene therapy delivery. The inner ear fluids and CSF are directly connected via the cochlear aqueduct which exhibits lymphatic-like characteristics. We developed a system to deliver viral construct to the inner ear using CSF. Real-time magnetic resonance imaging, computed tomography and optical fluorescence microscopy, showed that large CSF tracers reach the inner ear by dispersive transport via the cochlear aqueduct in adult mice. A single CSF administration of and adeno-associated viral vector transfected inner hair cells and rescued hearing thresholds and re-connected auditory synapses in a mice model for deafness, to a level comparable to wild-type mice.


First reported study using the CSF route for delivering gene therapy to rescue hearing in a mouse model. CSF can enter within minutes the inner ear and this easily accessible CSF route can deliver viral gene therapy to restore the function of an inherited mutation associated with deafness. Delivery system using cisterna magna injections are non-damaging to the cochlea when compared to the traditional direct routes such as the round window membrane injections or cochleostomy. Can be used to treat other disorders in the CNS.


Gene therapy for hearing and CNS disorders.

URV Reference Number: 6-22042A
Patent Information:
For Information, Contact:
Cynthia Zhang
IP Attorney
University of Rochester
Maiken Nedergaard
Barbara Mathiesen
Barbara Canlon
Christopher Cederroth