Despite the huge potential of new technologies to enable precision approaches to diagnosing, managing and treating genetic hearing loss, significant barriers and challenges to implementation remain. First and foremost, the complex heterogeneity of hearing loss conditions means that getting an accurate diagnosis can be a challenging process. This in turn impacts treatment development efforts, as, despite having high efficacy, the majority of gene therapy treatments are limited to treating highly specific variants within a single gene. In this blog, we explore key barriers to genetic hearing loss treatment.
Gene therapy delivery
Accurately delivering gene therapies to the cells where they are needed remains an ongoing challenge for some subtypes and variants. This is particularly pertinent when it comes to genetic hearing loss, as variants in just two genes, GJB2 and GJB6, account for more than 50% of severe-to-profound autosomal recessive nonsyndromic deafness in many populations around the world. GJB2, which produces connexin 26 protein, is estimated to be the cause of 30% of all genetic hearing loss in some populations. However, developing a gene therapy to tackle this commonly occurring variants has so far proved difficult.
Researchers have so far struggled to find an effective method for delivering a GJB2 gene therapy solely to the cells where it is needed. AAV vectors, commonly used in gene therapies to introduce a functioning copy of a gene to the relevant cells, have too broad an effect to successfully address connexin 26-linked hearing loss. Adding connexin 26 to ear cells where it is not needed causes damage to inner ear hair cells and an increased inflammatory response which has the potential to cause further damage to hearing.
Cracking the code of connexin 26-associated hearing loss therefore presents an unprecedented opportunity for researchers and organizations to deliver high impact therapies which have the potential to significantly change hearing loss outcomes for the majority of individuals living with hereditary hearing loss.
Cost and accessibility
Financial factors, including the incredibly high cost of gene therapy development, the long period between investment and return, as well as the high cost of approved therapies themselves, present a significant barrier to the successful delivery of precision treatments. With the average cost of developing a gene therapy estimated to be approximately $1.94 billion, and a single dose costing more than $4 million in some cases (while providing clinical benefit to only a limited number of patients), high initial outlay and the challenges of securing investment represent significant barriers to gene therapy use and development.
Developing business models such as risk-sharing agreements where organizations are guaranteed a return of funds if the expected results are not achieved is one potential solution to encouraging investment and development of rare disease treatments. There is also a significant financial incentive to invest in hearing loss research, as this is the most common sensory loss in the world and reported to affect approximately 40% of people with learning disabilities.
Additionally, despite the high initial cost of development, when the long-term effect of a one-off gene therapy is factoredin, the annualized price of treatment can often be comparable to, or even lower than, the cost of existing medicines and treatments which need to be administered on an ongoing basis.
Equitable access to gene therapies
Due to high costs and the specialist technologies required to develop and administer gene therapies, equitable access also remains a significant challenge for precision medicine treatments. Geographical disparity is a key factor. For example, up to twice as many babies are born with congenital hearing loss in sub-Saharan Africa than in other regions in the world. However, these countries are often poorly served when it comes to ear health and treatment services, despite being home to communities which are disproportionately affected by genetic hearing loss.
Developing collaborative global policies and building incentivizing infrastructure to encourage private investment in hearing loss research will therefore be fundamental to ensuring that future therapies are able to reach and benefit the communities and populations most in need.
Patient community pushback
While many individuals and families living with hearing loss actively pursue treatment and view the new developments in gene therapy with excitement, there are many Deaf individuals who view deafness and hearing loss as a cultural identity rather than a medical condition for which to seek a “cure.” For some, gene therapy presents a threat to Deaf culture and sign language, seeking to eradicate Deaf culture in favor of the norm of being a hearing individual in a world designed for hearing people. Deaf community members with this view cite that much gene therapy and medical research into hearing loss happens without consulting the Deaf and hearing loss community, and that hearing parents who have a child born with hearing loss are not given the option or the tools to effectively communicate with their child using sign language.
Gene therapies theoretically mean there could be an end to hearing loss without the individuals affected making hearing health decisions for themselves (for example, those using cochlear implants can make the decision to remove them, while children who receive gene therapy can’t reverse the intervention), meaning that Deaf culture and sign language could be made “obsolete” and that there would be no next generation of congenital non-hearers.
It’s therefore vital to exercise sensitivity around the development of gene therapies for hearing loss and to ensure the active involvement and feedback of diverse individuals and families from across the Deaf and hearing loss communities. Ensuring that community concerns are being addressed and working in close partnership with Deaf and hearing loss communities will help ensure that a range of voices and opinions are heard and that clinical trials are delivering meaningful solutions with real benefit to families, communities and individuals.
Key takeaways
The potential of precision medicine to transform the diagnosis and treatment of genetic hearing loss is undeniable. Advances in gene therapy, data-driven diagnostics, and novel treatment approaches offer hope for individuals and families affected by hereditary hearing conditions. However, realizing this potential requires overcoming significant scientific, financial, ethical, and societal challenges.
As we continue to push the boundaries of what is possible in precision medicine, it is critical to balance innovation with inclusivity, ensuring that breakthroughs in genetic hearing loss treatment benefit all those in need. To explore these challenges in more depth and learn how researchers are navigating them, download our whitepaper.
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