Common Supplement and Sildenafil Restore Cellular Signals in Lab Tests — May Reverse a Form of Inherited Hearing Loss

Researchers have identified mutations in a gene called CPD that appear to drive a form of inherited sensorineural hearing loss and shown, in laboratory models, that restoring certain metabolic signals can rescue affected cells. Early experiments using a common supplement (arginine) and the drug sildenafil (Viagra) corrected biochemical deficits in cells and partially reversed hearing-related damage in animal models, but experts caution this is not a ready-made treatment for people.

What the team found

Investigators first discovered CPD gene mutations in three unrelated families in Turkey where several members were born deaf. Analysis of larger genomic datasets also identified CPD alterations in other people with hearing impairment. CPD encodes the enzyme carboxypeptidase D, which the researchers found helps maintain levels of arginine, cyclic guanosine monophosphate (cGMP) and nitric oxide — molecules important for cell signaling in the inner ear.

Laboratory and animal evidence

When the CPD gene was switched off in human cells in vitro, arginine, cGMP and nitric oxide levels fell and cell stress and death increased. In mice, reduced nitric oxide and cGMP coincided with stress and loss of the inner-ear hair cells that convert vibrations into nerve signals. In fruit flies, silencing the CPD equivalent produced defects in the sensory organ used for hearing and balance.

Rescue experiments

Adding arginine to human cells restored nitric oxide levels and lowered cell death. The team also tested sildenafil, a drug that influences the nitric oxide signaling pathway, and observed partial reversal of some deficits in their experimental systems. These results support the idea that nitric oxide deficiency in the cochlea may be a key driver of this genetically defined form of hearing loss.

Nitric oxide is vital for many tissues and must be kept in a fine balance. — Dr. Mustafa Tekin

Important caveats and safety notes

The authors and outside experts emphasize several limitations. The study focused on a small, genetically defined subgroup and used human cells and animal models — not clinical trials in people. Sildenafil and other PDE5 inhibitors have rare but documented associations with sudden hearing loss and tinnitus, and the U.S. Food and Drug Administration has warned of possible hearing-related risks with this drug class. The researchers used sildenafil experimentally to probe the pathway and are not proposing it as a general hearing-loss therapy.

Implications and next steps

These findings point to a specific biochemical mechanism — impaired arginine/nitric oxide signaling — that could be targeted in future therapies for patients with CPD-related deafness. Further research is needed to validate the approach in human studies, to evaluate safety, and to develop treatments that precisely target the cochlea without systemic side effects. The lead author recommends genetic testing to identify the cause of unexplained hearing loss, since targeted approaches will depend on knowing the underlying gene defect.