gms | German Medical Science

In GMS Zeitschrift für Audiologie – Audiological Acoustics you will find a review article entitled “Restoring Hearing with Light” [1]. Tobias Moser provides our readers with a first-hand, comprehensive overview of the current state of research on optogenetic stimulation of the auditory pathway by the Göttingen team, which has been working on this project with remarkable dedication since 2007. Hopes and expectations are high. With the precise stimulation by light, an improved coding of the spectral information compared to the conventional cochlear implant (CI) should be possible and thus a significant increase in the quality of the transmission of speech and music should be achieved. However, the road to the desired goal of clinical testing is arduous: the efforts required for the development and testing of the proposed combination of gene therapy and medical device in a wide variety of research areas are extensive and must be intensified before entering the first clinical trial.

This provides an opportunity to look back at some of the ideas and concepts that have been pursued in the past, all of which have entered, or are still waiting to enter the clinical trial stage as alternatives to conventional hearing aids or simply to improve hearing in all kind of ways.

For example: “digital hearing aids”. The magic word “fully-digital” was first given as an attribute of a particular hearing aid innovation in 1995. In fact, by that time, high end hearing aids became mostly digitally adjustable, and the use of tiny screwdrivers to adjust miniature potentiometers, sometimes only inaccurately, became obsolete. However, the signal itself continued to be transmitted to the hard-of-hearing ear through conventional analog signal processing. The first fully digital hearing aid that could be worn on the ear in 1995 included an analog-to-digital converter and a signal processor as major innovations, thus laying the fundament for digital signal processing in hearing aids. The professional journals were not the only source of great expectations – it was hoped that digital technology would be as successful as in the domain of audio or video devices; the expectations of the persons affected by hearing loss were also very high. In fact, the progress achieved was initially rather modest. A considerable fraction of experienced hearing aid users have remained with their well-proven analog devices, and several additional years of development were needed before digital technology could meet expectations in the hearing aid sector.

Only a few years later (1997), the TICA (totally implantable cochlear amplifier) was introduced as another highly innovative concept for the treatment of sensorineural hearing loss. An engineer graduated from the Technical University of Munich, who had worked on piezoelectric transducers in his doctoral thesis, founded with a startup company with support of the ENT-Department of the Univ. of Tübingen (Prof. Zenner) the idea of bringing up a completely implantable hearing aid into clinical practice. Numerous obstacles and difficulties had to be overcome along the way. The coupling of the actual piezo transducer to the ossicular chain by means of a small connecting rod proved to be unexpectedly difficult, because feedback effects occurred. The eardrum, as a resonating structure, radiated sound in the direction of the implanted microphone, and as a countermeasure, the ossicular chain had to be interrupted surgically. These and many other difficulties finally led to the fact that the TICA system could not establish itself clinically.

Not only the TICA, but also many other fully or partially implantable hearing aid developments are now history. In addition to the “Carina” and the “MET” devices, whose development and patents were taken over by a well-known CI manufacturer, the promising direct acoustic stimulation of the cochlea by the “CoDACS” system is also no longer available on the market. For patients with a pronounced combined hearing impairment, this technology should be able to make better use of the inner ear residual function. Patients who are actually “too good” to be fitted with a CI no longer have this opportunity to stimulate residual hearing function. One can only speculate about the reasons why the companies no longer offer these interesting products. In general, the current funding opportunities for the direct transfer of innovative medical devices or gene therapies from basic academic research to clinical trials are insufficient.

In addition to developments in the field of technical management of hearing disorders, advances in the field of pharmacological or genetic research have repeatedly been a breeding ground for the hope of achieving restoration of hearing function through the development of drug treatments. Impressive progress has been made particularly in the field of gene therapy for sensory cell regeneration or repair. However, clinical investigation of gene therapy methods for hearing improvement is still in its infancy. The only trial to date in profoundly hearing impaired people using the recombinant adenovirus CGF166 and the transcription factor ATOH1 (hair cell differentiation) was initiated in the United States in 2014 and completed at the end of 2019. Although the side effects of the treatment were encouragingly modest, the unpublished results are not yet convincing. As can be seen from the results listed at “Clinicaltrials.gov”, not a single one of the treated hearing-impaired patients showed a clinically significant improvement in speech understanding or hearing thresholds. Similarly, stem cell therapy, which was also viewed with great expectations, has still not been studied in a human clinical trial. Whether defective hair cells can actually be replaced by new ones is therefore still written in the stars.

With the novel approach of optical stimulation of the auditory organ, a new perspective is now opening up for far-reaching improvements in hearing function. Unlike other innovations, such as the future gene therapy of a relatively small group of patients with a specific genetic defect, this is about improving hearing with an optical CI, i.e. a broadly applicable approach based on proven technology and surgery. I wish the project sufficient patience and the necessary luck in further development and testing. The preclinical data are promising and I am looking forward to the further results, especially the clinical trial, which can rely on the proven cooperation of dedicated patients, physicians and audiologists.

Uwe Baumann