Genetic deafness, new encouraging results from gene therapy

Replacing a defective gene with an injection. This is one of the strategies currently being tested to combat genetic deafness due to mutations in the Otof gene. It has been talked about for some time, and the latest results come from a study just published in Nature Medicine on 10 participants, including an adult of almost 24 years old and a teenager of 14 and a half years old.

A novelty, given that until now this type of gene therapy had only been tested on children. The results seem once again encouraging, even if the greatest benefits were observed in the 5-8 age group. The youngest and oldest instead showed more limited improvements.

From the ear to the brain

It is estimated that about half of cases of deafness in newborns have genetic origins. There are several genes involved, and one of these is the Otof gene, which codes for a protein known as otoferlin. When a sound reaches the inner ear, and in particular an organ known as the cochlea, it is converted into an electrical signal and transmitted to the brain through neurons. Otoferlin plays a role in this process of "transfer" of the signal from the ear to the brain, which is why pathological mutations of this protein cause congenital deafness.

Injecting the “working” gene

The idea, therefore, is to inject patients with genetic deafness due to mutations in the Otof gene with a “working” version of the gene itself. Through the injection, which is performed under general anesthesia, a solution containing one or more harmless viruses that carry the gene without mutations is introduced into the inner ear. In this way, the cells of the cochlea are put in the condition to be able to produce a working version of otoferlin.

As anticipated, this strategy has been discussed for some time and there are several clinical trials underway. As for the study just published in Nature Medicine , the trial was conducted at five Chinese hospitals, in collaboration with researchers from the Karolinska Institutet (Sweden).

Of the ten participants, eight were 8 years old or younger, and three were younger than 2 years old. Three participants received the injection in both ears, while the other seven received it in only one ear because of the presence of a cochlear implant in the other ear. Of these seven, one received two injections (in the same ear) 4 months apart.

Variable benefits

Overall, the therapy was well tolerated, and no participants (even those who received two injections 4 months apart) developed serious adverse reactions in the 6-12 months following the injection. The most common side effect reported was a reduction in the number of neutrophils, a type of immune system cell.

The benefits of the therapy were already noticeable one month after the injection, and at the six-month follow-up the minimum audible volume of the participants decreased, on average, from 106 to 52 decibels. The greatest benefits - as mentioned - were observed in the 5-8 age group, but even the older and younger ones showed some improvement.

Next steps

The reasons for the possible correlation between age and efficacy are not known at the moment. In general, the authors of the study themselves emphasize that these are preliminary results and that further research will be needed to validate them, especially given the limited number of participants. Furthermore, it will be necessary to monitor whether the benefits continue in the long term, given that these are therapies in the experimental phase.

In the meantime, the team is already thinking of using the same strategy for other genetic mutations that cause congenital deafness: “We and other researchers are extending our work to other more common genes that cause deafness, such as Gjb2 and Tmc1,” concludes Maoli Duan , one of the study’s coordinators. “These are more complicated to treat, but animal studies have so far given promising results.”