Scientists from Tel Aviv University say they have developed an “innovative gene therapy method” to treat impairments in hearing and balance caused by inner ear dysfunction.
Professor Karen Avraham, Dean of the Gray Faculty of Medical and Health Sciences, said the treatment constituted an improvement over existing strategies, demonstrating enhanced efficiency and held promise for treating a wide range of mutations that cause hearing loss.
Prof Avraham and Ms Roni Hahn, a PhD student from the university’s Department of Human Molecular Genetics and Biochemistry, led the study which was conducted in collaboration with Professor Jeffrey Holt and Dr Gwenaëlle Géléoc from Boston Children’s Hospital and Harvard Medical School.
Findings were reported in EMBO Molecular Medicine.
Prof Avraham said a wide range of genetic variants in DNA could affect function of the auditory system and the vestibular system, leading to sensorineural hearing loss and balance problems.
She said more than half of congenital hearing loss cases were caused by genetic factors.
“In this study, we aimed to investigate an effective gene therapy for these cases using an approach that has not been applied in this context before,” she said.
Hahn said gene therapy had emerged as a powerful therapeutic approach in recent years. One treatment strategy included use of engineered viral vectors, in which native DNA was replaced with a functional sequence of the target gene.
“These vectors utilise the virus’s natural ability to enter cells to deliver the correct gene sequence, thereby restoring normal function,” Hahn said.
‘Many gene therapies utilise adeno-associated viruses (AAVs) to introduce therapeutic genetic material into target cells, and AAV-based gene therapy for hearing loss is currently in clinical trials, showing promising early results.”
The researchers investigated a mutation in the CLIC5 gene, which is essential for maintaining stability and function of hair cells in auditory and vestibular systems. They said deficiency of this gene causes progressive degeneration of hair cells, initially leading to hearing loss and later resulting in balance problems.
The team used an advanced, structurally optimised version of an AAV vector called the self-complementary AAV (scAAV). They found this vector achieved faster and more efficient transduction of hair cells compared to traditional AAV methods, requiring a lower dose to achieve a similar therapeutic effect.
In treated animal models, the approach prevented hair cell degeneration and preserved normal hearing and balance.
“We applied an innovative treatment approach for genetic hearing loss and found that it improves therapeutic effectiveness while also addressing combined impairments in hearing and balance,” Prof Abraham said.
“We anticipate these findings will pave the way for developing gene therapies to treat a wide range of genetically caused hearing disorders.”
