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Assuming fix means cure, that’s not yet possible. Rather, effective treatment (Rx) is. Since reasons for deafness are multiple, genetic, toxic, noise- or age-related, one cure or Rx isn’t possible. Depending on underlying issue, electronic or biological are the two main approaches to treat deafness, with the former restoring hearing remarkably well.

Electronic Rx For Deafness

If only hair cells in the organ of Corti, the hearing organ, are damaged  but auditory neurons are intact, today’s state-of-the-art electronic deafness Rx is Cochlear implant (CI). Its genesis began in the 1950s with Andre Djourno (1904-1996) and Andre Strohl, a French surgeon and engineer team that 1st implanted an electrical stimulator to restore hearing, and with this pioneering technical innovation, laid down the  template others have followed since (1).

Backdrop to electronic Rx for deafness reveals a captivating against all odds story. The cochlea has >15000 sensory hair cells and ~30000 neurons. For long, leaders in otology staunchly believed that crude, external stimulation of peripheral neurons couldn’t possibly stimulate the cochlea, let alone that the brain could interpret such seemingly chaotic stimuli to result in hearing. Yet, against such formidable odds with a hostile culture distinctly acting against their favor, CI pioneers persevered and succeeded. As an editorial by Harry Levitt puts it (2),

Born in controversy.

Raised in dogged determination.

Matured in grace and glory.’

How does CI work? Long-term followup of CI patients reveals the ability to process and accurately decipher meager peripheral input improves dramatically over time, especially for sentences far more than for monosyllabic words (see figures below from 3).

Key insight from these studies is about brain function, i.e., when stimulus is apparently above a certain threshold of quality and quantity of information, the brain can ‘take over‘ and perform the necessary processing (3). Thus, more than anything, CIs unexpectedly reveal the unforeseen, potentially vast capacity of the brain to not only utilize but even more remarkably, make sense of sparse, external input. A game changer, this dramatically lowers the odds for similar therapeutic approaches for sight and sound, as well as other sensorimotor disabilities.

Offering an American perspective, Blake S. Wilson reasons basic research quickly made its way into the clinic in this instance due to the deliberate policy of these early pioneers to make all NIH-sponsored CI research freely available in the public domain. This allowed the ‘big three‘, i.e., Advanced Bionics, Cochlear Corporation and Med-El, the 3 largest CI companies with >99% of the world market, to quickly develop products incorporating the latest research (3). This has led to exponential growth in CIs since the mid-1990s (see figure below from 3).

These advances have been so remarkable that in 2013, 3 CI pioneers, Australian Graeme Clark (doctor), Austrian Ingeborg Hochmair, American Blake S. Wilson received the prestigious Lasker-DeBakey Clinical Medical Research Award. Tragically and utterly mystifyingly, the award strangely omitted the enormous crucial contributions of the French team led by Claude-Henri Chouard, who pioneered the world’s 1st multichannel CI in the late 1970s (4, also see figure below from 5).

According to Marcelo N. Rivolta (6), today’s cochlear implant consists of two major parts, an external head piece placed on the skin close to the temporal bone area. Containing a microphone and speech processor, it acts as a transmitter to process sound signals and is connected to a receiving coil which converts them into electronic impulses and delivers them through an internal cable to the 2nd piece, the internal cochlear electrode, implanted in the cochlea. ~22 electrodes winding through the cochlear scala tympani stimulate the SGNs (spiral ganglion neurons), the principal auditory neurons. These in turn transmit the signals to the brain via the auditory nuclei. Post-implantation, a patient can understand ~90% of words in quiet environments (7). However, post-operative rehabilitation is key for Rx to be effective.

All this good news aside, current CIs are still far from optimal. Apart from monosyllabic words, understanding complex sounds such as music, sound localization, tone languages (Mandarin Chinese for e.g. is famously a tonal language), these remain some unresolved hurdles (see figure below from 3).

As well, CI isn’t suitable for all types of deafness. For e.g., it doesn’t work for those whose auditory nerves don’t work. This led to the Auditory brainstem implant (ABI). Principle same as cochlear implant but bypasses SGNs by directly stimulating cochlear nucleus via surface-mounted ‘button‘ electrodes (8). Since ABI requires an electrode implanted directly into the brainstem, a substantially more invasive procedure (see figure below from 9), it’s not as prevalent. Plus it’s less effective compared to CI (8).

Biological Rx For Deafness

Biological Rx is still very much in its infancy. Genetic basis for hearing loss is extremely complex with ~500 genes involved (10). Most forms of hearing loss entail irreversible damage to hair cells or auditory neurons. Unlike those of fish, amphibians and birds, mammalian cochlear hair cells regenerate poorly or not at all (11), say after hearing loss due to noise (12). Idea of stem cell-based therapies is to coax various types of stem cells, embyronic, induced pluripotent or inner-ear, to differentiate in vitro into hair cell-like cells or sensory neurons (13). Theoretically two therapeutic approaches are possible, one much more technically challenging, namely, coax stem cells to fully differentiate in vitro into hair cells or sensory neurons and transplant them into the organ of Corti or alternatively, coax them to become progenitor cells that could differentiate into either hair cells or otic neurons or otic epithelium when delivered into the inner ear. Delivery is technically extremely challenging because few such cells transplanted into the inner ear successfully make their way into the organ of Corti while the majority die (10). As things stand as of Jan 2016, at least one clinical trial in children using infusion of autologous (from patient itself) stem cells derived from human umbilical cord blood cells is ongoing (14, Home – ClinicalTrials.gov identifier: NCT02038972).

Bibliography

1. Eisen, Marc D. “Djourno, Eyries, and the first implanted electrical neural stimulator to restore hearing.” Otology & neurotology 24.3 (2003): 500-506.

2. Levitt, Harry. “Cochlear prostheses: L’enfant terrible of auditory rehabilitation.” Journal of rehabilitation research and development 45.5 (2008): ix-xvi. https://www.researchgate.net/pro…

3. Wilson, Blake S. “Getting a decent (but sparse) signal to the brain for users of cochlear implants.” Hearing research 322 (2015): 24-38. Getting a decent (but sparse) signal to the brain for users of cochlear implants

4. Chouard, C-H. “The 2013 Lasker-DeBakey Clinical Medicine Research Award and cochlear implants: France unjustly overlooked…!.” European annals of otorhinolaryngology, head and neck diseases 2.131 (2014): 79-80. Elsevier: Article Locator

5. Mudry, Albert, and Mara Mills. “The early history of the cochlear implant: a retrospective.” JAMA Otolaryngology–Head & Neck Surgery 139.5 (2013): 446-453.

6. Rivolta, Marcelo N. “New strategies for the restoration of hearing loss: challenges and opportunities.” British medical bulletin 105.1 (2013): 69-84. challenges and opportunities

7. Spahr, Anthony J., and Michael F. Dorman. “Performance of subjects fit with the Advanced Bionics CII and Nucleus 3G cochlear implant devices.” Archives of Otolaryngology–Head & Neck Surgery 130.5 (2004): 624-628. http://citeseerx.ist.psu.edu/vie…

8. Moore, David R., and Robert V. Shannon. “Beyond cochlear implants: awakening the deafened brain.” Nature neuroscience 12.6 (2009): 686-691. https://www.researchgate.net/pro…

9. Lim, Hubert H., and Robert V. Shannon. “Two Laskers and Counting: Learning From the Past Enables Future Innovations With Central Neural Prostheses.” Brain stimulation (2014).

10. Müller, Ulrich, and Peter G. Barr-Gillespie. “New treatment options for hearing loss.”

11. Rubel, Edwin W., Stephanie A. Furrer, and Jennifer S. Stone. “A brief history of hair cell regeneration research and speculations on the future.” Hearing research 297 (2013): 42-51.  http://depts.washington.edu/rube…

12. Mcgill, Trevor JI, and Harold F. Schuknecht. “Human cochlear changes in noise induced hearing loss.” The Laryngoscope 86.9 (1976): 1293-1302.

13. Chen, Wei, et al. “Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.” Nature 490.7419 (2012): 278-282. http://www.ncbi.nlm.nih.gov/pmc/…

14. Safety of Autologous Stem Cell Infusion for Children With Acquired Hearing Loss

https://www.quora.com/Are-we-getting-close-to-being-able-to-fix-deafness/answer/Tirumalai-Kamala

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