Hearing loss and balance disorders are coupled both biologically and in their widespread impact. At Decibel, we are leveraging our multifaceted discovery platform to develop therapeutics that improve the lives of people with hearing and balance issues.
Hearing loss is one of the largest areas of unmet need in medicine and affects approximately 466 million people worldwide, including 48 million people in the United States.
In the U.S. alone, more than 30 million people have hearing loss in both ears, and 20 million experience tinnitus.
Hearing loss and tinnitus can be traced to myriad causes, including noise damage, genetics, ototoxicity from medications like cisplatin, and the normal aging process.
In people of all ages, regardless of cause, hearing loss and tinnitus can lead to chronic depression, social isolation, anxiety and sleep problems, as well as lost productivity.
Age-related hearing loss is a modifiable risk factor for cognitive decline and dementia.
There are currently no approved therapeutics for the treatment of hearing loss. Hearing aids and cochlear implants may offer benefits, but they fall short of replicating normal hearing function.
Sound waves travel through the air and into the outer ear canal where they cause the eardrum (tympanum) to vibrate. This causes a series of small bones (ossicles) to vibrate, which vibrates a small membrane called the oval window. This causes fluid inside the cochlea to move back and forth.
A portion of the cochlea known as the organ of Corti contains hair cells that convert this fluid movement into what our brain perceives as sound. There are two types of hair cells. Outer hair cells amplify quiet sounds, while inner hair cells primarily detect and transmit sound signals to the brain via the auditory nerve. There are roughly 3,200 inner hair cells and 12,000 outer hair cells in the human organ of Corti.
Outer and inner hair cells are arranged linearly within the cochlea tonotopic array. Hair cells at the base of the cochlea detect the highest frequencies. Those located at the apex, or tip, detect the lowest frequencies.
For normal hearing function, a variety of additional cell types and cellular structures must work together in concert. Broadly speaking, these include (but are not limited to):
Stereocilia: structures that project from hair cells and respond to movement of fluid within the cochlea, enabling the sensation of sound.
The stria vascularis: a group of cells that produce endolymph, a fluid in the cochlea that moves in response to sound waves.
Synapses: specialized connections that are required for the efficient transfer of sound information from hair cells to spiral ganglion neurons.
Spiral ganglion neurons: cells that transmit information from the cochlea to the brain, where sound is perceived.
Damage or dysfunction within any of these cells and cell structures can lead to symptoms of hearing loss, tinnitus or hyperacusis.
Approximately 8 million adults in the U.S. report chronic balance problems.
Loss of hair cells in the vestibular system is part of the aging process, and this loss is linked to impaired gait and increased risk of falls. These events often kick off a cascade of downstream problems, including impaired mobility, secondary falls, depression, and functional dependency.
People with bilateral vestibulopathy (BVP) – which is often caused by life-saving antibiotics such as gentamicin – may experience more dramatic loss of hair cells than elderly people. They may also suffer from far more significant symptoms, including a 31-fold increased risk of falling and a 70% incidence of oscillopsia (blurred vision occurring during head movement such as walking). Many affected are unable to drive and have difficulty with the activities of daily living.
There are currently no approved medications to restore balance.
The vestibular system, located in the inner ear, provides information critical for our sense of balance. This system includes five sensory organs – three semicircular canals and two otolith organs called the utricle and saccule – that work together to enable us to determine our position and movement in space. Importantly, the vestibular system also helps to stabilize and coordinate vision and provide input to our musculoskeletal system by way of the cerebellum, the brain’s movement control center.
The three semicircular canals are arranged on X-Y-Z axes. Each is responsible for a specific direction of head movement:
• Tilting upwards or downwards,
• Tilting to the right or to the left, and
• Rotating sideways.
Rotation is detected by vestibular hair cells, located within a sensory patch at the base of each canal called the crista. As our head rotates, the inertial movement of fluid in the canals displaces a structure that sits on top of the hair cells called the cupula. Cupular displacement deflects the mechanosensitive hair bundles on the hair cells, sending a signal to the brain via the vestibular nerve.
While the semicircular canals detect rotation, the saccule and utricle detect linear acceleration, for instance when you stand up, or speed up in a car. Analogous to the cupula in the cristae, the otolith organs contain small crystals called otoconia that sit atop hair cells. As we accelerate, these otoconia cause hair cells in the otolith organs to deflect, which in turn sends a signal to the brain.
As a result of the normal aging process, humans lose about half of our vestibular hair cells during the normal course of a lifetime, compromising our sense of balance; likely playing a significant role in the risk of falls. A small percentage of people can lose far more vestibular hair cells (up to 80%) in response to external insults such as aminoglycoside antibiotics. This dramatic loss has a substantial effect on balance and falls, and it can also impair one’s ability to stabilize vision during movement, also called oscillopsia.