Disabling hearing loss and other inner ear disorders affect more than 360 million people worldwide, with approximately one billion additional people at risk, according to the World Health Organization. Hearing loss is triggered by many factors, with ageing and noise exposure being two of the most common causes. Other causes include genetic conditions, complications at birth, specific infectious diseases (e.g., meningitis and measles), use of some medications, and chronic ear infections. There are varying levels of hearing loss, ranging from mild to profound, but it is widely accepted that an individual’s quality of life is greatly affected when it difficult to hear the common sounds that most of us take for granted. Not only is this detrimental to patients’ quality of life, it poses a heavy economic burden on the healthcare system in the range of $67 to as much as $107 billion.
The physiology of the inner ear, which contains the sensory organs responsible for both hearing and balance, and the delivery requirements it poses, is one of the major obstacles to overcome in developing new treatments for hearing loss and associated disorders. As the human inner ear is physically inaccessible, studying its normal function and pathology is difficult. .
To hear, soundwaves are channelled by the outer ear towards the bones of the middle ear and transformed into a force that pushes on a membrane (the oval window) in the cochlea. This force causes the fluid in the cochlea to move, thereby stimulating tiny sensory hair cells. Each hair cell corresponds to, and is activated by, specific frequencies. Signals from the activated hair cells are converted into nerve impulses and sent to the mid-brain, or the cochlear nucleus, via the cochlear portion of the auditory nerve, and then to the hearing portion (auditory cortex) of the brain. These hair cells do not regenerate when damaged. As hair cell populations decline, the ability to perceive certain frequencies diminishes, and hearing ability as a whole is reduced.
The vestibular system is the other part of the inner ear and is responsible for balance. It uses the same kinds of fluids and transducing sensory cells (hair cells) as the cochlea, sending information to the brain about the rotation and linear motion of the head and body.
There is no cure for hearing loss. Currently, patients are mostly treated with various types of assistive hearing technologies. Typical devices include hearing aids, assistive listening devices, cochlear implants and other implantable devices. These existing technologies may help patients to improve their overall ability to hear but do not restore full hearing ability. There are no approved drug treatments for hearing loss, providing a significant untapped market to the pharmaceutical industry.
Delivering drugs to the inner ear, whether local or systemic, is very difficult. The human ear has evolved to have very tight regulation over what can and cannot enter the cochlear and vestibular fluids of the inner ear. The architecture of the outer and middle ear, in addition to the presence of physical and semipermeable barriers, makes it structurally challenging for injection or droplets to reach the inner ear. On the other hand, the blood labyrinth barrier (BLB), separates the inner ear from most systemic circulation, and similar to the blood brain barrier (BBB), imposes significant limitations on the molecular entities that can reach the inner ear tissues. For this reason, it is critical that therapeutic approaches to addressing either vertigo or hearing loss are able to overcome the physical and/or physiological barriers to inner ear delivery.
The regeneration of new hair cell growth in the inner ear is an area of focus for development of both small molecules and gene therapy. Novartis is conducting a clinical study of a gene therapy, CGF166 in Phase 1/2 to deliver atonal gene transcription factor. The atonal gene, during embryonic development, induces differentiation of sensory cells in the inner ear. Meanwhile, Frequency Therapeutics is developing small molecules to restore auditory sensory cells. This approach stimulates inner ear progenitor cells to multiply and create new hair cells. As small molecules, the gene therapy can be formulated for direct injection into the middle ear where it then diffuses into the cochlea. &...
(All Rights Reserved)