Gene therapy research success in hearing-impaired mice provided "truly thrilling" moment



© ClaudioVentrella - iStock

Breakthrough UK lab mice research has provided strong evidence that gene therapy may one day be successful in restoring and protecting against human hearing loss caused by a common genetic defect.

That timing of intervention may be crucial is a key take-home from the study, which was funded by the Medical Research Council, Wellcome, and Decibel Therapeutics Inc., and carried out by the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London. Results suggest that early intervention would be critical to improvement in auditory function and protection of sensory hair cells from secondary degeneration.

And this hearing-oriented research could be extended to many other diseases using available mouse resources.

Spns2 mouse mutant behind particular hearing pathology

The King's College scientists used a genetic approach to fix deafness in mice with a defective Spns2 gene, a common form of pathology that involves a failure to maintain the local ionic environment of the sensory hair cells reflected in a reduced endocochlear potential. Spns2 gene transcription was activated at different ages in the mice after the onset of hearing loss. The researchers succeeding in restoring the mice's hearing abilities enough to give close to normal thresholds for an auditory brainstem response (ABR), at least at low to mid stimulus frequencies.

However, the theapy was found to be most effective when Spns2 was activated at a young age. Delaying the activation of Spns2 led to less effective recovery of ABR thresholds, suggesting that there is a critical period for intervention.

“Seeing the once-deaf mice respond to sounds after treatment was truly thrilling. It was a pivotal moment, demonstrating the tangible potential to reverse hearing loss caused by defective genes," said the study's first author, Dr. Elisa Martelletti.

The study's senior author, and Professor of Sensory Function at King’s IoPPN, Karen Steel, underlined the breakthrough nature of the research: "Degenerative diseases such as progressive hearing loss are often believed to be irreversible, but we have shown that at least one type of inner ear dysfunction can be reversed."

The research was published in the August 2023 issue of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Source: King's College, London/PNAS