Identifying therapeutic targets and test novel treatments that protect, restore and regenerate hearing

With our interdisciplinary team of discovery scientists and clinical experts at the UCLH Royal National ENT and Eastman Dental Hospital and University College London (UCL) Ear Institute we work towards the development of transformational hearing treatments tailored to the individual patient’s need.

Our researchers work closely with pharmaceutical and biotech companies to preclinically test new compounds and deliver trials of novel hearing drugs.

Subtheme leads:

Database of cohort of hearing loss

This document presents all available cohorts of hearing loss identified by our systematic review and grey literature search. It contains useful information on the variables contained within each cohort and contact information of authors. 

Achievements and key projects:

  • REGAIN –The REGAIN consortium of EU researchers successfully delivered the first trial worldwide of a locally administered drug aimed at regenerating inner ear sensory hair cells that are lost with age (funded by EU Horizon 2020).
  • QuicK+fire – Trial to evaluate a novel compound (voltage-gated potassium channel modulator) to improve hearing in adult cohlear implant users, particularly in challenging environments, such as background noise (funded by Autifony).
  • Soft-robotics system developed for inner ear therapeutic delivery (Patent application number: 2020301.4) - In this project we designed a fluid-driven soft robotic system which aims to increase patient-comfort during the injection by counteracting unwanted needle motion. It also reduces the cognitive load of the clinician by autonomously identifying sensitive regions in the ear and de-risks the procedure by steering the needle towards the desired injection site.
  • SeaSHeL– Working across 77 NHS Trusts the SeaSHeL study has recruited over 500 patients with sudden onset sensorineural hearing loss (SSNHL) to date. The study is delivered by the National ENT Trainee Collaborative INTEGRATE and aims to understand the impact of sudden hearing loss on quality of life (QoL) and to develop a prediction model that can help patients and clinicians make better treatment decisions.
  • Preparing for the Adoption of novel Therapeutics in Hearing loss (PATH) study- We have developed the first early health economic model for novel hearing therapeutics and are applying social science methodologies to develop a framework guiding the adoption and implementation of these therapeutics into the UK healthcare system (co-funded by NIHR ARC North Thames and Royal College of Surgeons of England).
  • NIHR Health Informatics Collaborative (HIC) in Hearing Health – The HIC was established to make better use of patient health data captured in NHS records and collect data in a standardised and integrated manner across UK sites. We have setup a structure for sharing and analysing these data anonymously. This will allow for:
    • exploration of the effects of known and novel risk factors such as disease clustering for hearing loss;
    • identification of the genetic causes of hearing loss;
    • definition of hearing loss sub-types;
    • identification of candidates who would benefit from upcoming clinical trials;
    • optimisation of patient benefit from individualised treatment strategies.
  • Ototoxicity – This project monitors hearing with novel out-of-booth hearing assessment technology and serum prestin levels as a biomarker for hair cell loss in sarcoma and testicular cancer patients receiving cisplatin (funded by the Royal National Institute for Deaf People).
  • Cochlear stress granules - a therapeutic target for auditory protection? – This project:
    • provides insight into the mechanisms underlying the inner ear hair cell response to stress,
    • tests whether stress granules are crucial factors for hair cell survival,
    • investigates whether they are a potential therapeutic target, and
    • derives novel, unbiased data on the critical components that are actively translated by hair cells in response to trauma.
  • Inner-Ear-On-A-Chip – This project has generated inner ear organoids containing hair cells, supporting cells and neurons from embryonic stem cells. Its translation will allow for the generation of a human Inner-Ear-On-A-Chip for the development of personalised hearing therapies through understanding hearing loss disease mechanisms and high-throughput screening of novel hearing drugs.
  • Regenerating human vestibular sensory hair cells using utricular explants – This project uses bioinformatic techniques analysing cellular transcriptomic data to identify potential molecular pathways underlying aminoglycoside-induced ototxicity. It uses RNA sequence data sets from whole human explanted utricles (part of the inner ear labyrinth) and isolated utricular sensory epithelia; several potential targets have been identified for further investigation.

PhD students:

  • Rishi Mandavia – Building a model of adoption for novel hearing therapeutics (supervisors: Anne Schilder, Carl May, Maroeska Rovers).
  • Natallia Kharytaniuk - Clinical and imaging biomarkers of audiovestibular function in infratentorial superficial siderosis (supervisors: Doris Bamiou, David Werring, Anne Schilder)
  • Simona Zingaro - Development of a stem-cell-derived inner ear organoid platform (supervisors: Jonathan Gale, Nico Daudet, Martin Birchall).
  • Jack Martin -  Stress granules in cisplatin ototoxicity (supervisors: Sally Dawson, Jonathan Gale).
  • Camilla Boscian - Regenerating hair cells in the human vestibular sensory epithelia. (supervisors: Dan Jagger, Jonathan Gale, Andy Forge, Martin Birchall).
  • Asma Awad – Study of Cisplatin-induced ototoxicity in adult and young people cancer patients; audiological monitoring, study of risk factors, and monitoring cochlear protein biomarkers. (supervisors: Shak Saeed, Anne Schillder, Nishchay Mehta) – Funded by RNID and a scholarship from the Libyan Government.

Key collaborators:

NIHR ARC North Thames, NIHR UCLH BRC Cancer Theme, Mental Health and Dementia themes. NIHR Manchester BRC, NIHR Nottingham BRC, Barts Health and Nijmegen University.

Recent publications:

Microscope lens