Making a difference - regenerative drug for hearing loss

Drug for hearing loss

New medicines to restore hearing loss: from molecular discovery to clinical trials

UCL Ear Institute researchers have unravelled a key molecular pathway to hearing loss. As part of an international consortium the UCLH BRC team took this discovery into the clinic and developed and trialled the first drug treatment worldwide aimed at restoring hearing. This new treatment was found to be safe and promising, a first step towards clinical use.

Most commonly, hearing loss occurs due to a progressive loss of sensory hair cells in the inner ear. In humans these hair cells do not naturally regenerate, so hearing loss progresses with age. Current treatment with hearing aids help people communicate, but they do not restore natural hearing or treat the underlying cause. 

UCL Ear Institute researchers were among the first to explain the role of a protein called Notch that plays an important role inner ear hair cell loss and regeneration1. Understanding this molecular pathway paved the way for teams to identify therapeutic targets and develop drugs that promote hair cell regeneration. 

The REGAIN consortium (REgeneration of inner ear hair cells with GAmma-secretase Inhibitors), supported by a €5,8 million European Commission Horizon2020 grant, developed a highly potent so-called gamma secretase inhibitor, which stops the Notch protein working and thereby ‘turns on’ the inner ear supporting cells to develop into new hair cells and restore hearing2.

The UCLH BRC team went on to design and lead the first ever in-human trial of a regenerative hearing drug. Adult patients with mild-to-moderate hearing loss recruited from across the UK, Germany and Greece were given three doses of the drug by injection into one ear and were followed-up with detailed hearing assessments for 12 months, demonstrating the medicine was safe and promising.

The team are also advising global biotech and pharmaceutical companies how best to design and deliver trials of new hearing therapies and, together with NIHR ARC North Thames have developed a framework that applies health economics and behavioural science to help healthcare services prepare for their future implementation3.

References

  1. Daudet N et al. Dev Biol. 2009
  2. Schilder AGM et al. Hear Res. 2019
  3. Mandavia R et al. Otol Neurotol. 2020