Health, UK (Commonwealth Union) – UCL and UCLH researchers have achieved a significant milestone by completing the inaugural trial of a therapy engineered to address hearing loss. Dubbed the REGAIN trial, its outcomes, detailed in Nature Communications, mark the pioneering exploration of a treatment dedicated to reinstating lost hearing. Central to this trial was the investigation of a compound known as gamma secretase inhibitor LY3056480.
Researchers of the study pointed out that though the therapy didn’t universally restore hearing among adults with mild to moderate hearing impairment, a closer examination of the results revealed promising shifts in various hearing assessments among select patients, indicating a degree of efficacy in the inner ear.
These promising signals of effectiveness underscored the necessity for further refining LY3056480, leveraging the insights gleaned from this trial.
Participants in the trial, ranging from 18 to 80 years old and hailing from the UK, Germany, and Greece, exhibited mild to moderate hearing loss. Fifteen individuals partook in the phase 1 trial, which established the safety and tolerability of the treatment, while 44 participants engaged in the phase 2a trial, aimed at evaluating the drug’s efficacy.
Study participants underwent three injections of the drug directly into the ear, administered through the eardrum. Their auditory capabilities were evaluated through various tests both before and after the drug administration.
One examination focused on the faintest detectable sounds participants could perceive, while another gauged their capacity to comprehend spoken words amidst background noise—a prevalent challenge for individuals grappling with hearing impairment.
At the 6 and 12-week marks following the treatment initiation, 45% of participants demonstrated an ability to discern sounds at least 10 decibels softer than their previous threshold.
Nevertheless, the research team established a more stringent criterion to gauge the drug’s efficacy—an average enhancement of 10 decibels or greater across three distinct sound frequencies. Regrettably, the observed improvements in hearing during the trial fell short of meeting this ambitious benchmark.
Researchers of the study underscored the point that hearing loss stands as the predominant sensory ailment among humans, presenting a substantial gap in therapeutic options. It chiefly stems from the progressive deterioration of sensory hair cells or their functionality within the inner ear. Presently, the sole recourse is the utilization of hearing aids, which facilitate communication but do not restore natural auditory function or address the underlying causes of hearing impairment.
As individuals age, hearing loss progresses due to the inability of inner ear sensory hair cells to naturally regenerate.
Historically viewed as irreversible, damage to these hair cells may potentially be reversed according to various studies conducted in animal models. These studies suggest that a gamma secretase inhibitor, a small molecule substance, holds promise in regenerating functioning inner ear sensory hair cells.
The groundbreaking REGAIN trial (Regeneration of inner ear hair cells with gamma secretase inhibitors) was spearheaded by Professor Anne GM Schilder from the UCL Ear Institute, in collaboration with UCLH Royal National ENT, Eastman Dental Hospitals, NIHR UCLH Biomedical Research Centre, clinical partners in Germany and Greece, and the company Audion Therapeutics. This trial marked a significant milestone as the first investigation of a regenerative hearing drug globally.
Professor Schilder says “There are many important lessons from this study which will guide future studies of its kind. For example, the study will help how we best select the patients that may benefit from these new and highly targeted hearing treatments.
“This requires a better understanding of the mechanisms behind inner ear hearing loss and better hearing tests to identify its causes in patients. Big data and AI may speed up this process.”
To advance this initiative, the UCLH BRC team, alongside other BRCs, has established the NIHR Hearing Health Informatics Collaboration (HIC). This collaboration aims to aggregate anonymized hearing data from NHS hospitals nationwide for analysis using advanced computational methods.
On a local level, the team has launched a new patient registry named HEDGE. This registry provides individuals with hearing loss the chance to engage in research aimed at uncovering the genetic and environmental factors, molecular pathways, and mechanisms contributing to hearing loss.
The significant interest from patients to participate in research was demonstrated through REGAIN.
Professor Schilder says “We were contacted by more than 5,000 patients with hearing loss worldwide requesting to take part, illustrating the huge unmet clinical need.”
