matsuyuki / Flickr
New research has found that mutations in the CPD gene are associated with congenital hearing loss, and arginine and sildenafil help reverse and prevent the damage.
A new published in the Journal of Clinical Investigation found that mutations in the CPD gene can cause a rare and hereditary form of congenital hearing loss, disrupting essential molecular pathways that protect the sensory cells of the inner ear.
The findings pave the way for potential new therapies using existing medications, including Viagra.
The study links the CPD gene, previously known to modify proteins, to sensorineural hearing loss (SNHL), an inherited condition usually diagnosed in childhood and considered irreversible for a long time. Although devices such as hearing aids and cochlear implants can improve hearing, there is currently no approved medical treatment that addresses the underlying biological cause.
The investigation began when researchers identified shared mutations in the CPD gene in three unrelated Turkish familiesaffected by congenital deafness. Analysis of genetic databases later revealed that other individuals with CLD variants also had early-onset hearing loss, reinforcing the gene’s link to hearing function.
To understand how CPD influences hearing, scientists performed experiments in mice and fruit flies, which share similar inner ear structures and neurological pathways with humans. Tests have shown that the CPD gene helps maintain levels of arginine, an amino acid used to generate nitric oxide, a neurotransmitter essential for nerve signaling. When mutations in the CPD gene interrupted this process, oxidative stress increased, leading to death of sensory hair cells, which are tiny structures in the inner ear that detect sound vibrations.
“DPC maintains arginine levels in hair cells to enable a rapid signaling cascade through nitric oxide,” explained lead author Rong Grace Zhai, PhD, of the University of Chicago. “When this pathway is interrupted, hair cells become vulnerable and die.”
It is important to note that the team identified two potential treatments. Arginine supplementation helped restore cellular balance, while sildenafil (Viagra), a medication that increases nitric oxide signaling, improved cell survival and reduced hearing loss behaviors in experimental models. Both strategies reversed aspects of the damage in patient-derived cells and in fruit flies, explains .
The researchers plan to explore how frequently CPD gene mutations occur in the general population and whether isolated variants may also contribute to age-related hearing loss or other sensory disorders.
