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This discovery not only identified the genetic cause, but also led to the development of two promising treatment approaches, one of which is based on a well-known drug, Viagra.
This discovery is the result of a collaborative research effort between the University of Chicago, the University of Miami, and scientific institutions in Turkey. The researchers followed three unrelated Turkish families suffering from hereditary sensorineural hearing loss, a permanent form of hearing loss typically diagnosed in early childhood. While hearing aids and cochlear implants can improve hearing, there is currently no medical treatment that addresses the underlying cause of this condition.
Through in-depth genetic analysis, researchers discovered that these families share specific mutations in the CPD gene, a gene known for its role in protein modification. Crucially, a review of genetic databases revealed that other individuals carrying mutations in this gene also exhibited signs of early hearing loss, further strengthening the gene's link to hearing function.
In an attempt to understand the mechanism of action of this gene in depth, the team conducted experiments on mice and fruit flies, and revealed a precise mechanism in which the CPD gene produces an enzyme responsible for generating the amino acid arginine, which in turn helps in the production of nitric oxide - a crucial neurotransmitter responsible for transmitting signals across the nervous system.
When mutations occur in this gene, this pathway is disrupted, leading to oxidative stress and the death of the fine sensory hair cells in the inner ear responsible for detecting sound vibrations.
Professor Rong Grace Chai, the lead researcher in the study, explains the mechanism behind this discovery, saying: "Our research shows that the CPD gene works to maintain the appropriate level of arginine within hair cells, which allows for the acceleration of the chain of nerve signal transmission through the production of nitric oxide. This mechanism explains why, although this gene is present in many other cells across the nervous system, the hair cells in the inner ear are the most affected and vulnerable to any defect in the CPD gene."
What is most exciting about this study is the researchers' success in identifying two treatment approaches: the first uses arginine supplementation to compensate for the deficiency caused by the gene mutation, and the second uses sildenafil (Viagra) to stimulate pathways affected by the nitric oxide deficiency. Both approaches showed positive results in improving cell survival and reducing hearing loss behaviors in laboratory models.
This scientific breakthrough not only reveals a new cause of hereditary deafness but also opens new avenues for treatment. It highlights the value of fruit fly models in studying neurological diseases, including age-related conditions, giving researchers the ability to understand nervous system disorders and identify potential therapeutic approaches.
The research team now looks to expand the study to gain a deeper understanding of the nitric oxide signaling pathway and its role in the inner ear's sensory system, as well as to study the prevalence of CPD mutations in larger populations and to investigate whether these mutations represent a risk factor for other types of sensory impairments, which could pave the way for new treatments for broader types of hearing loss.
