Gene Therapy Advancements Offer Hope for Deafness Treatment
New tests, shown in The Lancet magazine , present an advance in cases of gene therapy for deafness. The study was published in Science magazine and found that some of the hearing had recovered in children born with mutations that left them deaf.
OTOF gene
The treatment mentioned in the articles only involves cases of deafness related to a mutation in the otoferlin gene, also known as OTOF. In this sense, professor Victor Evangelista de Faria Ferraz, from the Faculty of Medicine of Ribeirão Preto (FMRP) at the University of São Paulo (USP), explains that the protein produced by the OTOF gene has an important role in conducting the electrical signal to the nerve and make the signal reach the brain.
“Otoferlin is linked to nerve conduction in the cochlea, the organ that transforms mechanical sound into nerve impulses to the brain. Specifically, it is present exactly in hair cells, cells that transform the mechanical signal into an electrical one”, adds Ferraz.
Regarding the case of deafness linked to the gene, Professor Miguel Angelo Hyppolito, from FMRP-USP, comments: “It generally affects children right from birth, but it can manifest itself later. In some conditions there is severe sensorineural hearing loss and then the person does not hear anything and is currently treated with a cochlear implant.”
Gene therapy
With results published in The Lancet and Science magazines , an innovative gene therapy treatment for OTOF-related deafness was tested. “The studies are still at a very early stage. But it is clear that the research group publicizes this ‘initial success’ for propaganda reasons, for the opportunity to be the first to carry out a genetic treatment, without detracting from the entire importance of this first result for science”, explains Hyppolito.
The professor also explains that, as it only involves a single gene and there is no damage to the cochlear hair cells — at the beginning of the picture —, the studies began with this specific type of deafness. He also comments that most hearing losses involve damage to external or internal hair cells in the organ of Corti that would need to be regenerated, something very difficult as it involves the manipulation of several genes.
Ferraz explains how the treatment worked: “It was possible using a modified type of virus, an adeno-associated virus, which does not cause disease, containing a functional copy of the gene, injected directly into the cochlea. Otoferlin begins to be expressed in the necessary cells, with hearing improvement in five of the six patients who underwent the treatment described in this article.”
Despite this, Ferraz also points out that there was difficulty in placing the OTOF in a single adeno-associated virus, due to its size. To resolve this, one of the strategies used was to divide the gene in two, using two viruses for the process, a step that, according to the specialist, was fundamental to the success of the therapy.
Carlos Frederico Martins Menck, professor at the Institute of Biomedical Sciences (ICB) at USP, explains that the treatment, for now, is still temporary. “The expectation, for this adeno-associate, is that this expression will last a few years, I would say two to three years. So, there will probably have to be a reapplication in the future. It may be temporary, but we will learn this, we will see it in the future and with the use of it”, he declares.
And the future
Menck also mentions the possibility of the treatment reaching the Brazilian Unified Health System in the future: “Eventually, it could be approved by the Brazilian Anvisa, perhaps depending on more studies, and then it could be commercialized. Some gene therapy processes are already being commercialized in Brazil, but the cost is extremely high.”
In the professor’s expectation, with an increase in the number of processes that mainly use this type of adeno-associated virus — as there was enormous progress during the pandemic in the use of viruses carrying genes —, the price and cost of treatment could be reduced.
Miguel Hyppolito, however, shows a different point of view: “I don’t think I’m going to see that happen. The SUS deprives patients of many treatments, as, in the case of the hearing network ordinances, they have been out of date since 2011. Unfortunately, the principles of the SUS are not applied, only on paper and in political propaganda”. He also states that, if it occurs, it should be in the distant future.
Regina Célia Mingroni Netto, professor at the Biosciences Institute (IB) at USP, explains that the treatment, through gene therapy, is not yet applied by any Brazilian hospital or research center and represents a small percentage of deafness cases. Furthermore, she also says that it is important to carry out genetic tests on children and young people with deafness, being able to identify possible candidates for gene therapies — in the case of the current research, those with alterations in the OTOF gene.
“It would be very interesting if genetic tests to identify genes altered in deafness became more accessible. In Brazil, there are very few genetic reference centers that have the capacity to provide these tests. This expansion through public hospitals in the network accredited and financed by the SUS would be very important, so that we can prepare the ground for gene therapy”, he informs.