Targeted Treatments for Congenital Hearing Loss Discovered
Approximately 3 in 2,000 people are born with hearing loss, a condition that poses lifelong challenges for many individuals. However, recent breakthrough research has identified three genetic mutations responsible for a rare form of congenital auditory impairment, opening up the possibility of targeted treatments that could include the use of common supplements and the erectile dysfunction drug sildenafil, known commercially as Viagra.
These mutations were pinpointed by an international team of researchers who conducted extensive gene sequencing and identified affected individuals from three unrelated families in Türkiye. All of these individuals had sensorineural hearing loss and rare variants in the CPD gene, which encodes an enzyme called carboxypeptidase D.
Upon uncovering these genetic mutations, the researchers delved deeper into their implications for health and explored potential therapeutic interventions. They discovered that a common dietary supplement could potentially help repair some of the damage caused by these mutations.
Neuroscientist Rong Grace Zhai from the University of Chicago expressed excitement about the study, stating, “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.”
The research revealed that the mutations in the CPD gene disrupted the production of the amino acid arginine, leading to decreased levels of critical compounds like nitric oxide and cyclic guanosine monophosphate (cGMP). Without sufficient arginine, nitric oxide levels drop, impacting signaling in the nervous system and causing stress and death in the sensory cells of the ear, particularly the hair cells essential for hearing.
Further investigations using fruit flies with CPD-like gene mutations confirmed inner ear damage, hearing loss, and balance issues. Zhai explained, “CPD maintains the level of arginine in the hair cells to allow a quick signaling cascade by generating nitric oxide, making these hair cells more sensitive to the loss of CPD.”
Preliminary experiments involving the addition of arginine showed reduced cell death and restored nitric oxide levels, indicating a potential role for the dietary supplement L-arginine in addressing certain forms of hearing loss. Additionally, the drug sildenafil, which boosts cGMP signaling, emerged as another potential treatment avenue.
Future studies will explore the biological pathways impacted by CPD gene mutations and conduct similar tests on larger cohorts. The researchers have already identified these mutations in other individuals with hearing loss, underscoring the potential significance of these findings for developing gene therapies to address cellular damage underlying deafness.
Zhai emphasized the importance of repurposing FDA-approved drugs for treating rare diseases, stating, “It is a good example of our efforts to repurpose FDA-approved drugs for treating rare diseases.”
The study has been published in the Journal of Clinical Investigation.
