An international team of scientists took a key step in understanding the congenital deafness: they discovered that certain genetic mutations can trigger a rare type of hearing loss hereditary. The finding not only explains the mechanism responsible for this condition, but also points out possible ways to reverse its effects.
The researchers, from the University of Chicago, the University of Miami and several institutions in Turkey, analyzed cases of hearing loss present from birth in unrelated families. From this work, they identified the genetic alteration responsible and proposed two innovative strategies that could transform the approach to this disease.
According to the results published in the Journal of Clinical Investigationmutations in the CPD gene affect hearing by altering the functioning of sensory cells of the inner ear. According to the report, the discovery began when researchers observed an unusual combination of mutations in three Turkish families suffering from sensorineural deafness, an inherited condition that causes permanent hearing loss from childhood.
According to the doctor Rong Grace ZhaiJack Miller Professor for the Study of Neurological Diseases at the University of Chicago, The research allowed us to establish a direct relationship between the CPD gene and hearing loss.
In this sense, he explained that the gene, initially known for its function in protein modification, also plays a decisive role in the generation of the amino acid arginine and, as a consequence, in the synthesis of the neurotransmitter nitric oxide. In the inner ear, These elements are essential for nerve signaling and the protection of the cells responsible for capturing sound vibrations.
The study revealed that when the CPD gene suffers mutationsthe production of arginine and nitric oxide is reduced. This deficiency triggers oxidative stress and the death of hair cells, vital for sound perception.
According to experiments carried out on mice, CPD deficiency directly affects the functionality of auditory cellsweakening the ability to process sound signals. Furthermore, the researchers identified that the damage persists despite the use of external amplifiers such as hearing aids or cochlear implants, since the injury occurs at the cellular level.
The relevance of the connection between the gene and deafness was strengthened after analyzing international genetic databases. According to the data, people carrying different mutations in CPD also presented early onset deafness, which reinforces the relationship between this gene and auditory functioning.
According to the authors of the study, this knowledge is essential because, until now, sensorineural deafness was considered irreversible and without medical treatment options directed at the cause.
Another innovative aspect of the work involved the development and evaluation of potential treatments. According to the experiments carried out in animal models, particularly in fruit flies, the researchers tested two strategies. One of them consisted of administer arginine supplements to compensate for the deficiency caused by the genetic defect.
The other use was sildenafilknown commercially as Viagra, which stimulates one of the signaling pathways altered by the drop in nitric oxide. Both alternatives improved the survival of auditory cells derived from human patients and attenuated the deafness symptoms detected in animal models.
Dr. Zhai explained that the advance not only provides details about the molecular mechanism of this type of deafness, but also suggests a concrete therapeutic strategy. According to his words, The study highlights the usefulness of taking advantage of medications approved by regulatory agenciesoriginally developed for other diseases, in the treatment of rare pathologies such as these hearing disorders.
The research showed the value of simple animal models for analyzing complex human diseases. Fruit flies, for example, facilitated the understanding of the cellular processes involved and the development of experimental treatments.
According to the authors, this type of experiments not only serves to study hereditary disorders, but also to analyze diseases related to aging.
In the following phases, The researchers plan to examine the frequency of CPD mutations within broader populations. According to the team, they seek to determine what proportion of people could have variants in this gene and its relationship with other forms of hearing loss, including those associated with age. They will also evaluate the role of nitric oxide in the sensory functionality of the ear and its possible incidence in various sensory neuropathies.
CPD and nitric oxide appear as the new protagonists in the understanding of hereditary deafness. This research opens a concrete possibility of functional recovery in affected patients, thanks to the development of targeted therapies based on identifiable molecular mechanisms.
