Around 3 in 2,000 people are born with hearing loss, a condition often considered irreversible. New research suggests this may not always be the case, identifying specific genetic mutations linked to a rare form of congenital deafness – and potential treatments involving the erectile dysfunction drug sildenafil (Viagra) and a common dietary supplement.
The Genetic Link to Deafness
An international team of researchers pinpointed three mutations in the carboxypeptidase D (CPD) gene. These mutations were found in three unrelated families from Türkiye, all exhibiting a congenital form of sensorineural hearing loss. The discovery emerged from an extensive gene sequencing process designed to uncover the biological roots of this specific type of deafness.
How the Mutations Cause Hearing Loss
The CPD gene encodes an enzyme critical for maintaining levels of the amino acid arginine. The identified mutations disrupt arginine production, leading to a cascade of cellular damage within the inner ear. Specifically, reduced arginine levels inhibit the production of nitric oxide, a vital signaling molecule in the nervous system. Without sufficient nitric oxide and its downstream effects on cyclic guanosine monophosphate (cGMP), sensory cells in the ear become stressed and die, particularly the delicate hair cells responsible for hearing.
Evidence from Animal and Cellular Models
Researchers confirmed these findings through studies on human skin tissue, engineered mice lacking a functional CPD gene, and even fruit flies with similar genetic defects. All models demonstrated consistent signs of inner ear damage, including hearing loss and balance problems.
Potential Treatments: Viagra and L-Arginine
The team discovered that supplementing with L-arginine restored nitric oxide levels and reduced cell death in laboratory settings. Even more promising, the drug sildenafil (Viagra) – known for enhancing cGMP signaling – showed similar protective effects.
“This study is exciting because we found a new gene mutation that’s linked to deafness, and more importantly we have a therapeutic target that can actually mitigate this condition,” says neuroscientist Rong Grace Zhai from the University of Chicago.
Repurposing Existing Drugs
The findings suggest that existing, FDA-approved drugs could be repurposed to treat rare forms of deafness. This approach accelerates the path to treatment, bypassing the lengthy and expensive process of developing entirely new medications.
Future Research
The team plans to analyze biological pathways affected by the CPD gene and conduct larger-scale human studies. Initial analysis of a UK genetic database already suggests these mutations are present in other individuals with hearing loss.
“What makes this really impactful is that not only do we understand the underlying cellular and molecular mechanism for this kind of deafness, but we also found a promising therapeutic avenue for these patients,” says Zhai.
This research represents a significant step toward treating genetic deafness, offering hope for individuals with this debilitating condition. The potential to repurpose existing drugs could expedite treatment and improve the lives of those affected
