Auditory Neuroscience and Optogenetics

Considering that approximately five percent of the world’s population requires treatment of hearing impairment there is a major unmet clinical need for improved hearing restoration beyond current hearing aids and cochlear implants. Therefore, we are working with marmoset monkeys for late preclinical studies on gene therapy and optical cochlear implants which builds on pioneering work in rodents performed at the Institute for Auditory Neuroscience of the University Medical Center. We chose to work with marmosets as a non-human primate model that is amenable to genetic manipulation, has a rich vocal communication and also for this reason has attracted interest of auditory neuroscientists. We have established virus administration and cochlear implant surgery as well as physiological and behavioral analysis of hearing in marmosets. 

In collaboration with the Behr lab (ref. for GFP marmoset) we are working toward modelling human genetic hearing impairment. We are currently focusing on auditory synaptopathy caused by mutations in the OTOF gene that encodes for the hair cell protein otoferlin. There is great hope that OTOF-related hearing impairment can be cured by AAV-mediated gene therapy based on partial restoration of auditory function in mouse models (Al‐Moyed et al., 2019; Akil et al., 2019; Rankovic et al., 2021). Nonetheless, much remains to be done to translate these approaches into a clinical application. We aim to contribute to this important effort by first optimizing the gene therapy approach in mice and then translating it to the newly generated marmoset model OTOF-related hearing impairment.

The cochlear implant, used worldwide by more than 700.000 hearing impaired people, typically enables open speech understanding and is considered the most successful neuroprosthesis. Nonetheless, listening in noisy environments as well as music appreciation remain challenging mostly because of the poor frequency and intensity resolution that results from broad current spread from of each of the one to two dozens of electrode contacts (see image above: Electrical Cochlear Implant). Since light can be conveniently confined in space, using optogenetic stimulation of the spiral ganglion of the cochlea promises a fundamental improvement of frequency and intensity coding compared to that achievable with electrical cochlear implants. In our preclinical work with rodents and marmosets, we are developing gene therapy and optical cochlear implants for future clinical optogenetic hearing restoration. Collaboration with academic partners in Freiburg and Chemnitz as well as with industry (OptoGenTech and MED-EL) is of paramount importance to accomplish this task.