Every time we stand upright, turn our heads, or take a step, a small organ in the inner ear keeps us steady. This organ, called the utricle, senses head movements and maintains balance. But when its delicate sensory hair cells are damaged by injury, illness, or even medications like certain antibiotics or chemotherapy drugs, people can experience debilitating dizziness, instability, and falls that profoundly affect daily life.
Despite millions of people worldwide living with balance disorders, there are currently no approved treatments to repair or regenerate the utricle. Studying the adult human inner ear is incredibly difficult, leaving scientists without the cellular roadmap needed to develop therapies.
New research from Sunnybrook Research Institute offers the most detailed view of how the adult human balance organ responds to damage, opening new avenues for future treatments.
Mapping the Utricle
A new study in Nature Communications led by Dr. Emilia Luca, a research associate in Dr. Alain Dabdoub’s lab at Sunnybrook Research Institute, used utricles donated by patients undergoing surgery to understand this essential balance organ better. The team, comprised of members of the Dabdoub lab and surgeons, Drs. Joseph Chen and Vincent Lin from Sunnybrook’s Department of Otolaryngology generated the most comprehensive gene map of the utricle’s cells, revealing how the organ responds within 24 hours of injury.
Their analysis uncovered a surprising diversity of supporting cells, the “non-sensory cellular guardians” that surround and protect the sensory hair cells and may facilitate their regeneration. The researchers identified six distinct types of these supporting cells, each with its own gene signature. They also identified more than 400 genes whose activity changes in response to a damaging drug.
“We now have a molecular blueprint of how the adult human utricle responds immediately after injury,” says Dr. Luca. “This gives us clues about which cells might be capable of responding to damage and how we might one day activate them.”
The First Responders
One of the most exciting findings in the cell map was the identification of two supporting cell clusters that may act as first responders. These cells express genes involved in tissue repair, inflammation control, and cellular remodelling. They are located near areas where other cells are missing, and near newly-formed hair cells, suggesting they may be the utricle’s repair crews.
“These findings highlight previously unknown genes and potential drug targets,” adds Dr. Alain Dabdoub, senior author of the study and a senior scientist in the Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute and the Koerner Chair in Hearing and Balance Regeneration. “They could give us a roadmap for developing therapies for balance disorders and potentially hearing loss.”
Looking Ahead
“This collaborative work between our researchers and ENT surgeons will also result in a detailed protocol, planned for submission early this year, as a resource for scientists and clinicians interested in studying vestibular organs,” says Dr. Dabdoub, also a professor in the Departments of Otolaryngology, Head and Neck Surgery, and Laboratory Medicine and Pathobiology in the Temerty Faculty of Medicine at University of Toronto.
This research also demonstrates the power of hospital-embedded science. The utricles used in the study were donated by Sunnybrook patients undergoing tumour removal surgery; no animal models were used, and this type of study is difficult to reproduce in non-hospital-based laboratories.
The team is now building a comprehensive human gene atlas of the inner ear organs, a dataset that will accelerate discoveries across the field.
“These discoveries bring us one step closer to therapies that could improve inner ear disorders,” adds Dr. Luca, also an elected chair of the International Association of Italian Researchers in Canada.
The study was supported by grant funding from the Canadian Institutes of Health Research, the Hearing Health Foundation’s Hearing Restoration Project, the University of Toronto, Department of Otolaryngology, Harry Barberian Research Fund, the Japan Society for the Promotion of Science Postdoctoral Fellowship, Canadian Graduate Scholarship, Masters Program from CIHR, Ontario Graduate Scholarship, Doctoral Award, Raymond H. W. Ng Graduate Scholarship, and support from the Michael and Sonja Koerner Charitable Foundation.