Hearing and balance disorders are both permanent, irreversible conditions in humans. In fact, hearing loss is the most common sensory disorder around the world. Normally, sound vibrations are transmitted from an object through the air to your ear. Vibrations of the ear drum cause bones in your middle ear to vibrate. These vibrations then pass into the most inner component of your ear to the hearing organ (cochlea). The most common problem underlying hearing loss and deafness is the irreversible loss of sensory hair cells of the cochlea, the molecular basis of which is poorly understood. Worst of all, there are currently no biological therapies to treat hearing loss or balance disorders.
Hearing loss and balance disorders can be caused by either environmental factors or genetic inheritance. Usher syndrome is the most common condition that affects two of the major senses—hearing and vision—but also leads to disorders in a third sense—balance. It is inherited in an autosomal recessive manner, so someone must receive a mutated form of the syndrome from each parent. One of the mutations that causes the most severe form of Usher syndrome is a single change in one’s DNA from guanine to adenine (c.216G>A).
In a recent study published in Nature Biotechnology, titled, Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c (2017), Pan. et al. aimed to use gene therapy to treat this genetic cause of auditory (hearing) and vestibular (balance) dysfunction. Although other scientists have demonstrated proof-of-principal experiments to suggest that gene therapy could be used to treat genetic deafness, the results have never been able to match the sensitivity of a healthy inner ear. Mouse models are commonly used to investigate and better understand biological disorders, and Pan et al. used mice with the exact same causal mutation of Usher syndrome (c.216G>A), which also causes the same symptoms as seen in humans. Without modifying any of the normal chromosomes of the mouse, the authors put the normal non-mutated Usher gene onto a very small piece of circular DNA that originally comes from bacteria, inserted that into a recently created virus vector, and locally injected this virus (Anc80L65) into the inner ears of newborn mice. Could this be enough to fix the problem?
Pan et al. reassessed these mice at 6 weeks of age and found a recovery of Usher expression on both the gene and protein level. More importantly, they showed that the recovery of these inner ear hair cells leads to significantly improved auditory and vestibular function such that they were both fixed to nearly normal, healthy levels. Relative to other previous attempts to improve auditory function, these authors showed a 1000-fold improvement in hearing sensitivity and thus the most complete rescue of auditory function for any application of inner ear gene therapy. Although much more work needs to be done before translating this work into the clinic and testing this virus on humans, this work is strong evidence that biological therapies can be used to treat genetic causes of human deafness and balance disorders.