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Targeting challenges of active ageing: innovative integrated strategies for the healing of age-related hearing loss

Final Report Summary - TARGEAR (Targeting challenges of active ageing: innovative integrated strategies for the healing of age-related hearing loss)

According to the World Health Organisation, more than 360 million people worldwide suffer from hearing loss ( Approximately one third of the population over 65 years old is affected by age-related hearing loss, also known as presbycusis, making it the second most common cause of disability in older people. There is no restorative treatment for deafness but functional replacement by means of prosthesis. Therefore, prevention and treatment of hearing loss is an unmet medical need.

The general objective of TARGEAR has been to develop a collaborative strategy between public research institutes and private companies, based in the transfer of knowledge to design and implement preclinical and clinical studies for presbycusis. A second general objective has been to contribute to the formation of researchers in the experimental design, transfer and translation of knowledge in the field of hearing loss. The long-term objective has been to develop a stronger biomedical research in hearing loss for a better future for the deaf people. TARGEAR partners have complementary experience in the study of presbycusis. UNIFI (Italy), BIOMED (Czech Rep.) and CSIC (Spain, coordinator) focus their research in animal and cellular models of hearing loss to develop translational strategies from the bench to the clinical practice. The Medical School (UAM) and “La Paz” Hospital-IdiPAZ (Spain), CSIC team, has offered clinical training and expertise. AFFICHEM (France) synthesises AF243 (a small bioactive molecule) and MED-EL (Austria) manufactures innovative hearing implant solutions.
MED-EL personnel received training in basic hearing research and neurobiology of hearing (CSIC and BIOMED), as well as in clinical practice (CSIC-La Paz), joint work involving all secondees has been published or is in preparation (1). BIOMED has been very active in the training of secondees from MED-EL, collaborating with CSIC at different levels, and organizing training schools (1). BIOMED and MED-EL have ongoing projects to further develop some of the ideas generated during TARGEAR to better understand hearing electrophysiological data. Dr. Huesers, recruited and then employed by MED-EL, cooperated with Dr. Lassaletta (CSIC- La Paz hospital) to develop a hearing diagnostic tool for patients with questionable nerve functionality. This included development of a new disposable electrode array (MED-EL) and verification in neurinoma patients during tumour removal surgery. CSIC, BIOMED and UNIFI researchers have visited MED-EL to develop research at the company. MED-EL also developed intrasectorial collaboration with Affichem, by combining the electrode-coating silicone with AF243. The study of the properties of the drug liberation from silicon carried out by UNIFI secondee at MED-EL and at Affichem premises provides bases for a potential future use of this molecule in human implants. Results suggest that AF243 released from silicon shows low otoprotection activity. Further work will be required to confirm the potential use of dendrogenins to increase the efficacy of cochlear implants. The MED-EL workshop “Effective translation of research results to the clinical practice” covered the most important aspects of applying novel research ideas into the implantable medical devices area. Presentations of consortium partners provided examples of current research topics with a potential to be translated into future clinical products. Affichem has also actively participated in intersectorial personal exchange (with UNIFI, CSIC and BIOMED) and organised training activities. It can be highlighted the incremental number of outreach activities performed the company (1) and the 2017 Special Public Prize won on the “European Health Catapult” competition. Dr. Caron, recruited and then employed by Affichem, has carried out an intense activity within the action organising a variety of activities for TARGEAR. So far no joint publications have been prepared, being some of the joint results (CSIC and UNIFI) under evaluation for know-how protection. UNIFI recruited Dr. Guevara, the role of this partner has been to understand basic molecular mechanisms of inner ear biology. They have focused in the study of the receptor for a small lipid (SP1) that holds potential as a novel pharmacological target (1). UNIFI specialised within TARGEAR in the study of otic cell lines, collaboration with CSIC is ongoing to further advance knowledge in the field and will hopefully help to individuate new molecular targets to prevent hearing loss. In this connection, CSIC, BIOMED and UNIFI have submitted a proposal to the H2020-PEOPLE-ITN-ETN program to further develop the ongoing collaboration. CSIC has carried out inter- and intrasectorial collaborations with all partners. Dr. Cervantes, CSIC recruited, used her extensive cell biologist experience to carry out key work to test bioactivity of otoprotection (IGF-1, synthetic AF243, etc.) and to develop research on new biocompatible vehicles for drug delivery to the inner ear (publication in preparation). CSIC has also carried out work to contribute to the identification of the genetic and molecular bases of age-related hearing loss (1). The CSIC team has received the Hearing Deficiency Research Award from the Spanish Confederation of Families of Deaf Persons (FIAPAS). Finally, CSIC has coordinated the action and organised scientific and outreach events, as well as training activities (1).
The use of several European languages on the website and social networks has made possible to achieve greater dissemination of TARGEAR and reach sectors of the population that do not normally receive quality scientific information (1).

We have targeted the following specific objectives and achieved the results indicated below:
1. Further identified the stages and molecular elements of the damage and repair processes involved in age-related hearing loss (1).
2. Improved the experimental design of preclinical studies in animal models of human hearing loss. CSIC and BIOMED have standardised studies in animal and cell models required to undertake preclinical studies (Standard Operating Procedures).
3. Tested the potential of synthetic molecules to protect and repair otic cells and to prevent hearing loss in animal models. Affichem has synthetized the molecule AF243, CSIC and UNIFI/MED-EL have tested biological activity in different experimental settings.
4. Transfer of knowledge from research centres to industry in the field of age-related hearing loss. CSIC and BIOMED have transferred knowledge to MED-EL and all the basic research partners have visited Affichem.
5. Improved the design of electrophysiological procedures to understand sound central processing by sharing knowledge among company experts, basic and clinically-oriented researchers (Lassaletta et al. Otol & Neurotol 2017 Dec;38(10):e413-e420).
6. Improved the professional career of young scientists, clinicians and engineers through training periods in industry and academia-hospital environments in the field of hearing loss (1).
7. Increased public awareness about caring for hearing and promotion of social awareness on the consequences of hearing loss (1).

In summary, we have contributed to a healthy auditory aging by: i) further understanding the genetic and molecular basis of presbycusis; ii) studying bioactive molecules and testing an electrodiagnostic tool; iii) raising social awareness on hearing loss and cognitive decline; and iv) training young professionals. The main expected final results are: i) to build a competitive ERA in presbycusis and active ageing with professionals trained to work in different environments; ii) to implement the use of the intraoperative electrode in the clinical practice; and iii) to raise awareness on the importance of hearing care for healthy cognitive ageing. The potential impact of these results is clear as the number of people with presbycusis is increasing steadily as the European population ages.

(1) Newsletter December 2017 (
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A version of the publishable summary, including TARGEAR´s logo and graphics, has been attached.