Congenital deafness refers to a chronic condition of deafness that is present in children at birth. It is one of the most common birth defects in children, estimated to be affecting approximately 2-3 children in every 1000 births. These hearing losses can be either sensorineural or conductive.Sensorineural hearing loss refers to a permanent type of hearing loss that is due to an auditory nerve being malformed or damaged in the inner ear – the cochlea; whereas conductive hearing loss is where the affected area is the middle – tympanic cavity – or outer ear – the auricle or external auditory canal, which is usually treatable. However, a recent joint China-U.S study conducted between Fudan University (Shanghai, China) and Mass General Brigham (Massachusetts, U.S.) in 2022, showed that gene therapy may be the answer to treating congenital deafness entirely. The research shows great promise, and if you are a U.S. healthcare worker, enrolled in online FNP programs, or simply want to learn more about this breakthrough, then this article will be your handy guide. Otoferlin is a protein in humans that is encoded by the OTOF gene. It was first discovered in 1999when it was found that mutations of the OTOF gene caused nonsyndromic deafness, or in other words, partial or total hearing loss that has no direct association with physical abnormalities of the ear. The general conclusion was that the causes of these forms of deafness are traced to a mutation of the OTOF, which is called DFNB9. The characteristics of DFNB9 consist of a failure to produce a proper otoferlin protein, which is required for transmitting sound or sound signals from the cochlea to the brain. Clearly, this protein is fundamental to functional hearing and auditory processing in humans. Without otoferlin, while sound can be translated into electric signals, it will still never reach the brain to process.
As the root cause of deafness is traced to DFNB9 and a mutation of the OTOF gene, it also means that it is an attractive target for gene therapy. Currently, there are no drugs that have been approved by the Food and Drug Administration (FDA) to treat hereditary deafness, so gene therapy presents a potentially viable prospect as a future treatment method. It is also a relatively simple condition, as it is only a single mutation and involves no physical abnormalities or damage to the cochlea.
Researchers at the Eye & ENT Hospital of Fudan University conducted a 26-week observation trial period on the six children. The Mass Eye and Ear partners introduced an adeno-associated virus (AAV), which is essentially a viral vector technology used specifically for gene therapy, carrying a human OTOF gene into the inner ears of the six children. The level of doses of the viral vector differed between each patient depending on the levels of their deafness. At the beginning of the trial, all six children were deaf. This was evidenced by an average auditory brainstem response (ABR), a test for hearing nerve sensitivity and brain response to sound signals, of over 95 decibels; the normal level is generallybelow 25 decibels. After the 26 weeks, it was demonstrated that five children had significant hearing recovery. They showed a 40-57 decibel reduction in the second ABR test since the introduction of the AAV, dramatic improvements in speech recognition, and restored abilities to engage in normal conversation. In total, about 48 adverse events were observed during this period, with an overwhelming majority (96%) being low-grade adverse events, and the remaining being either transitory or reversible with no long-term effects and impacts. This is proof that children can have a sound future safely and effectively through gene therapy and its treatment of DFNB9.
Due to its proven effectiveness and safety by the joint China-U.S study, trials of this gene therapy are slowly being rolled out to the general public.
During October 2023, clinical researchers at CHOP, just like in the previous trial, administered an AAV containing a copy of the OTOF gene into Dam’s ear. The gene therapy was placed in Dam’s inner ear via an endoscope as it allowed the eardrum to be lifted through a small entry point into the cochlea. Then a single small dose of the AAV containing the OTOF gene was introduced directly into his inner ear.
CHOP since then has had two further patients enrolled for treatment– a 3-year-old boy from Miami and a 3-year-old girl from San Francisco, both of whom will be treated in one ear while the other ear has been filled with cochlear implants. Both trials have shown there has been promising hearing recovery through this method of treating congenital deafness or hearing loss. The growth of gene therapy has been tremendous, offering itself as a potential one-time treatment for conditions such as congenital deafness for the future – but it is also the potential that the many children who suffer from these conditions can also finally enjoy the melodies of their own future.