Identification of new pharmacological strategies and mechanisms of action for the therapy of Menière´s disease in vivo.

• Applicant: Professor Dr. Martin Canis
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 220462641

Menière´s disease is the second frequent form of peripher vestibular vertigo. As a probable pathophysiological cause an endolymphatic hydrops is discussed. Leading symptoms are recurrent attacks of vertigo, acute hearing loss and tinnitus. Primary treatment goals aim to prevent these attacks and in consequence persisting audiological and vestibular deficits. Prophylactic effects have been described for betahistine a Histamine-H1-receptor-agonist and H3-antagonist. However, betahistine is used only on empirical basis since experimental or even mechanistic data is missing. In the present project we therefore aim to identify new therapeutic strategies for Menière´s disease and mechanisms of action on cellular level. To this end, the regulation of cochlear microcirculation and possibilities of pharmacological interventions are planned to be investigated by 1-photon-intravitalmicroscopy. Furthermore, regulation of terminal vessels is supposed to be analysed on cellular levels by 2-photon-microscopy (intracellular Ca2+ in pericytes and fibrocytes of capillaries, capillary leakage). Functional parameters such as hearing threshold and vestibular evoked myogenic potentials will be further analysed after therapeutic interventions in a chronic hydrops animal model. In regard of the severe symptoms and the large number of patients, new therapeutic options and further insights into the pathophysiological background would be of great clinical and socioeconomic interest.

• DFG Programme: Research Grants