Mini RNA sequences to repair hearing?

Professor Brigitte Malgrange and her team have for many years been seeking a way to repair “damaged ears”, that is to say, to enable individuals who have all but lost their hearing to recover at least part of it. Several results have been published in the last few years and the most recent - pulishced in Cell Reports (1) - show the role played by microRNAs in the production of hair cells for the first time. It is now even be possible to envisage reproducing these microRNAs in order to treat certain types of deafness…

Many factors can cause loss of hearing: genetics, complications during pregnancy or childbirth, ototoxic medicines taken by a pregnant woman… These causes are congenital. Apart from these factors, deafness can occur for example, after an infection, after taking ototoxic medicines (anti-carcinogens, antibiotics…), exposure to excessively high levels of sound, ageing… (See article Regenerating cells in the inner ear )

Hearing deficiency can be attributed to the destruction of hair cells, or to problems with the auditory nerve itself. This type of deafness is known as neurosensory deafness. The production of hair cells is what interests Professor Brigitte Malgrange, head of the Development Neurobiology Unit at the GIGA-Neurosciences. We know that when cells have been destroyed for the reasons mentioned above, they are never replaced in humans. Because auditory information is no longer detected and transmitted to the brain, the individual concerned is affected by perceptive deafness. This demonstrates the importance of being able to restore hair cells…

The role of microRNAs

Professor Malgrange’s team discovered that microRNAs, small fragments of RNA, do not code for proteins, as their bigger counterparts do, due to their small size. “These mini RNA sequences were discovered around fifteen years ago and between 1500 to 2000 of them have been identified up to the present. But their role is not insignificant: these microRNAs prevent the production of certain proteins by attaching themselves to the part of the RNA involved in their synthesis. They are not specific however: that is to say that each one of them can prevent the production of between two-hundred to three-hundred proteins! And this can have implications for hearing, because it has already been established that certain microRNAs are located in the inner ear and can help us to understand the molecular mechanisms involved in the initial development of hair cells”.

The supporting cells, together with hair cells, make up the organ of Corti, which forms the cochlea. “However, inside the organ of Corti initially, the two types of cells are differentiated. We have therefore tried to better understand these original differentiation mechanisms to try to reproduce them, in order to generate new hair cells”, explains Professor Malgrange.

For this purpose, a mouse was deprived of an enzyme which enables the synthesis of microRNAs: Dicer. “In this mouse that was deprived of RNA, we noticed that the cochlea was poorly-developed; we identified a microRNA (miR-124) which we knew played a role in the differentiation between the supporting cells and the hair cells”. This microRNA was therefore identified as being very likely to play a role in this differentiation.

This is the first time that it has been possible to identify the role of a microRNA in the differentiation of cells in the organ of Corti, and this paves the way for a possible regeneration by stimulating the mechanism comparable to that which is produced during their initial formation.

(1) Aurélia Huyghe,Priscilla Van den Ackerveken,Rosalie Sacheli, Pierre-Paul Prévot, Nicolas Thelen,Justine Renauld,Marc Thiry, Laurence Delacroix, Laurent Nguyen, and Brigitte Malgrange, MicroRNA-124 Regulates Cell Specification in the Cochlea through Modulation of Sfrp4/5, Cell Reports, september 2015.