Researchers have investigated if dietary arginine supplements and the erectile dysfunction drug sildenafil (Viagra) can help those with a rare gene mutation causing congenital or early-onset deafness.
The study indicated the ‘simple treatments’ may help restore cellular function and reduce cell death in the ear.
Dietary arginine supplements are concentrated forms of L-arginine, an amino acid that can help improve circulation by increasing nitric oxide production, which widens blood vessels.
Researchers from the University of Miami Miller School of Medicine in the US and collaborators from Turkey and the US said they had uncovered “a potentially treatable genetic cause of hearing loss” and offered a new avenue for treatment.
Dr Mustafa Tekin, professor and chair of the university’s Dr John T. Macdonald Foundation Department of Human Genetics led the study which was published in the Journal of Clinical Investigation on 30 September 2025.
The team said it had identified rare mutations in a gene which produces the carboxypeptidase D (CPD) enzyme that is essential for the survival of cochlea cells.
They identified the mutations in several people from three unrelated families with congenital or early-onset deafness.
The mutations disrupt the enzyme’s ability to process arginine. They were more common in people with hearing loss than in the general population, based on data from the 100,000 Genomes Project.
In their cellular studies, patient-derived fibroblasts (cell types in connective tissue) showed reduced levels of arginine, nitric oxide and cyclic guanosine monophosphate (cGMP), a messenger molecule. This led to increased oxidative stress and cell death.
Supplementing these cells with arginine restored nitric oxide and cGMP levels and reduced cell death, the researchers said on the Miller School of Medicine website.
They also found CPD was widely expressed in the mouse cochlea. Silencing CPD in mouse cochlea cultures triggered cell death, which could be partially rescued by arginine supplementation.
Additionally, flies lacking the CPD ortholog (“silver” gene), which makes pigment granules, exhibited structural and functional defects in their hearing organs, impaired auditory transduction and abnormal movement behaviours. Feeding the flies arginine or sildenafil improved their sensory and motor functions.
Overall, the CPD mutations disrupted hearing, the researchers said. But unlike most genetic forms of hearing loss, which were typically irreversible, the study showed simple interventions, such as dietary arginine supplements or sildenafil medications that boost cGMP signalling, could restore key cellular functions and reduce cell death in the ear.
Genetic testing could help identify who may benefit but more studies were needed, they said.
