Deafness: reading DNA opens a door to unprecedented treatments

For years, traditional diagnoses confirmed hearing loss but could not explain why. "Without the cause, treatment is decided blindly," says Adrián Turjanski, a researcher at CONICET and scientific director of the GEN360 test. By revealing the exact reason, science was able to trial a therapy designed for that problem and not for "deafness" in general.

The importance of reading DNA

The developmental progress and the precarious clinical studies at birth allow for the detection of certain anomalies in the early years of life. “In the case of children who cannot hear, the signs appear early: they do not respond to voice, do not turn to a sound, language development is halted. Classic studies confirm profound hearing loss but do not explain why,” says Adrián Turjanski.

This is where genetic tests play a fundamental role due to their ability to read large sets of genes. Currently, they assist in decision-making regarding nutrition, disease prevention, metabolism and macronutrients, relative cardiometabolic risk signals, among others. “Modern tests do not promise magical certainties, but they offer personal evidence to make better decisions,” emphasizes Turjanski. He adds: “just like in this research, we must first understand biology and then choose the action.”

Designing the correct therapy

This is where sequencing comes into play. “A simple test is enough to transform the letters of the genome into data. With bioinformatics, those data are compared to a reference and variants (changes) that explain the condition are sought,” suggests the researcher. In these children, the laboratory finds the same culprit: biallelic mutations in OTOF, the gene that encodes otoferlin, a key protein for the inner hair cells of the ear to “deliver” the sound signal to the auditory nerve.

Identifying the defect in the OTOF gene allowed clinical and industry teams to test a local gene therapy, DB-OTO. "The logic is simple to say and complex to do: a 'functional' copy of the gene is placed in the ear so that the inner hair cells can start producing the protein again and restore sound transmission," details Turjanski. This precise intervention, related to cochlear implant surgery, is performed through intracochlear infusion using an AAV1 vector.

The results of this recent trial reflected clinical improvements in hearing in 11 of the 12 participants (from 10 months to 16 years). In fact, some of the treated patients achieved normal hearing within weeks.

First, molecular diagnosis, then action and precise intervention. That order —sequence, understand, intervene— not only applies to a cutting-edge trial, it is already part of everyday practice. The lesson goes beyond the therapy itself: “without reading DNA, that door would not have opened,” concludes the representative of GEN360.