Researchers linked a rare form of congenital sensorineural hearing loss to mutations in the CPD gene that reduce arginine production and lower nitric oxide and cGMP signaling. In cell cultures, CPD‑deficient mice and mutant fruit flies, hair cells in the inner ear became stressed and died. Supplementing L‑arginine restored nitric oxide and reduced cell death, while sildenafil (Viagra) boosted cGMP signaling and also showed potential. Results are preliminary and require clinical trials, but they point to repurposable treatments and further study.
Viagra and L‑Arginine Show Promise for Reversing Cellular Damage in a Rare Form of Congenital Deafness
Researchers linked a rare form of congenital sensorineural hearing loss to mutations in the CPD gene that reduce arginine production and lower nitric oxide and cGMP signaling. In cell cultures, CPD‑deficient mice and mutant fruit flies, hair cells in the inner ear became stressed and died. Supplementing L‑arginine restored nitric oxide and reduced cell death, while sildenafil (Viagra) boosted cGMP signaling and also showed potential. Results are preliminary and require clinical trials, but they point to repurposable treatments and further study.
09:27 PM, 11/13/2025Health
New research links CPD gene mutations to a treatable form of congenital hearing loss
Around 3 in 2,000 people are born with some form of hearing loss, most of which is currently considered permanent. An international research team has identified three rare mutations in the gene encoding carboxypeptidase D (CPD) that cause a particular form of congenital sensorineural hearing loss and suggests existing treatments—including the supplement L‑arginine and the drug sildenafil (marketed as Viagra)—may help reverse the cellular damage in laboratory models.
What the researchers found
Using extensive gene sequencing, investigators traced the mutations to individuals in three unrelated families from Türkiye who all shared congenital sensorineural hearing loss and rare CPD variants. Follow-up experiments in human tissue and animal models explored how these mutations harm hearing.
Analyses of human skin cells and cochlear tissue from mice engineered to lack functional CPD revealed that the mutations reduce production of the amino acid arginine. Levels of downstream signaling molecules, notably nitric oxide and cyclic guanosine monophosphate (cGMP), were also decreased. Because arginine is a precursor for nitric oxide, its reduction undermines normal signaling in inner‑ear hair cells, increasing cellular stress and leading to the death of the short hair bundles essential for detecting sound.
The team also examined fruit flies with mutations in CPD‑like genes; these insects showed hearing and balance problems consistent with inner‑ear dysfunction, strengthening the link between CPD loss and auditory impairment across species.
"It turns out that CPD maintains the level of arginine in the hair cells to allow a quick signaling cascade by generating nitric oxide," said neuroscientist Rong Grace Zhai of the University of Chicago. "Although CPD is expressed broadly in the nervous system, hair cells are especially vulnerable to its loss."
Therapeutic implications
In cell and animal experiments, supplementing with L‑arginine restored nitric oxide levels, reduced cellular stress and lowered rates of hair‑cell death. Separately, sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor that enhances cGMP signaling, also mitigated cellular damage in model systems. These findings point to two potential, repurposable therapeutic avenues: correcting arginine deficiency or boosting the cGMP pathway.
The researchers emphasize these results are preliminary. Experiments to date have been conducted in cell cultures, CPD‑deficient mice and fruit flies, not in human clinical trials. The team has, however, identified the same CPD variants in additional individuals with hearing loss by querying a large UK genetic database and plans broader studies to map the affected pathways and evaluate treatments in larger patient cohorts.
Context and cautions
Efforts to develop gene therapies for hereditary deafness are already underway, and this work adds mechanistic insight into one specific genetic cause. While L‑arginine and sildenafil are established and widely used compounds, they carry risks and their safety and efficacy for this form of hearing loss have not been proven in humans. Clinical trials will be required before any treatment recommendations can be made.
Publication: The study appears in the Journal of Clinical Investigation.