Researchers at the University of California-San Francisco (UCSF) have made a groundbreaking discovery in audiology by identifying a gene linking deafness to cell death in the human inner ear. This advancement has the potential to lead to novel approaches in preventing hearing loss, a widespread condition impacting millions globally, caused by factors such as exposure to loud noise, aging, and specific medications.
Drugs inhibiting UPR process could prevent hearing loss
The study establishes a connection between studies on hearing impairment in animals and a unique hereditary deafness variant in humans. The focal revelation centers on the TMTC4 gene. Aberrations in this gene initiate a phenomenon referred to as the unfolded protein response (UPR), resulting in the demise of crucial cells within the auditory system known as hair cells.
According to the UCSF team, the UPR process is triggered in hair cells by loud noise or drugs such as cisplatin, indicating its potential role as a common factor in different types of deafness. They emphasize that certain drugs inhibiting the UPR have successfully prevented hearing loss in lab animals, prompting the need for human trials to assess their effectiveness in preventing hearing impairment.
Many American adults experience hearing loss annually due to factors such as aging and noise exposure. According to Dr. Dylan Chan, co-senior author of the study, there has been uncertainty about the underlying causes of hearing loss. The study reveals conclusive evidence identifying TMTC4 as a human deafness gene and emphasizes the potential of targeting the Unfolded Protein Response (UPR) to prevent deafness.
TMTC4 mutations induce hair cells destruction
In 2014, Dr. Elliott Sherr, a co-senior author at UCSF, initiated a discovery process after noticing mutations in TMTC4 in young patients with brain malformations. Subsequent animal studies, particularly with mice carrying TMTC4 mutations, initially appeared normal but eventually lost their hearing as they matured.
The collaborative work of Drs. Sherr and Chan revealed that TMTC4 mutations induce self-destruction in hair cells. They discovered that ISRIB, a drug created at UCSF to inhibit the Unfolded Protein Response (UPR) in brain injuries, effectively prevented hearing loss in animals exposed to noise.
