These two animal studies report on potential new applications for intra-tympanic OTO-104, a slow-release hydrogel formulation of dexamethasone that is currently being used in a Europe-wide randomised trial for Ménière’s disease. In the first paper, guinea pigs were given a single bilateral dose of OTO-104 one day prior to loud noise exposure. In the control and lowest dose OTO-104 groups, hearing loss was observed; this was not the case in the high-dose OTO-104 group in whom hearing was preserved. The protective effect was still seen when the OTO-104 was given two or three days after acoustic trauma, but not after four days. In the second of the papers, a single dose of OTO-104 was injected bilaterally one day prior to a single high dose of cisplatin, or was given weekly for three weeks, 30 minutes prior to lower-dose cisplatin administration. The cisplatin doses were calculated to be equivalent to those used in human clinical practice. In both conditions, the OTO-104 was found to be oto-protective. The higher dose (6%) appeared to offer a greater protective effect than lower doses. In both studies, standard aqueous dexamethasone was not seen to have any therapeutic effect. In addition, co-administration of OTO-104 with the gluco- and mineralo-corticoid antaganoist mifepristone appeared to negate any of the protective effects, allowing the authors to conclude that the action of OTO-104 is on classical nuclear receptor pathways. Caution must be used in interpreting the results of these early studies in small numbers of animals. However, the results are interesting and will undoubtedly prompt further studies in humans. 

The sustained-exposure dexamethasone formulation OTO-104 offers effective protection against noise-induced hearing loss.
Harrop-Jones A, Wang X, Fernandez R, et al.
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Stephen James Broomfield

University Hospitals, Bristol, UK.

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