They can hear well up to around the age of 40, but then suddenly people with DFNA9 are deaf. Inner ear cells are no longer able to reverse the damage caused by a genetic defect in their DNA. Researchers at Radboud University Medical Center have now developed a “gene patch” for this type of genetic deafness, through which they can eliminate hearing cell problems. More research on animals and humans is needed to bring the genetic correction to the clinic as a treatment.
Genetic deafness can appear in different ways. Often a genetic defect (mutation) causes deafness immediately after birth. Sometimes, as with DFNA9, you experience initial hearing problems after forty, fifty, sixty years. This has to do with the way DFNA9 operates mechanically. Everyone gets half of their genes from their father and the other half from their mother. If you have two healthy copies of the DFNA9 gene, your inner ear is functioning normally. If you receive a modified copy of the gene from your father or mother, deafness will develop later in life.
Erik de Vries and Erwin van Wijk, both researchers in the Division of Hearing and Genetics in the Department of Otolaryngology, have conducted extensive research on the condition. De Vrieze: “We now know that you actually produce enough DFNA9 protein bound to only one healthy gene copy to be able to hear well for life. But there is a problem with this condition. The mutated protein, somehow, disrupts the function of a healthy protein. , So that a healthy protein also cannot do its job.Inner ear cells are constantly removing this clumping protein, but after decades the cleaning service in these cells has reached its limits and is no longer able to handle these protein clumps.The limit value has been exceeded. Waste builds up, and hearing cells start to function poorly and even die over time. After years of normal hearing, DFNA9 patients suddenly notice that their hearing deteriorates, and sometimes it deteriorates very quickly. Even at some point they will become deaf. ”
Enough time for treatment
The DFNA9 mutation appears to have originated from a common ancestor in the southern Netherlands, somewhere at the end of the Middle Ages. This can be inferred in one form or another from the prevalence of the somewhat unique clinical profile, which is now estimated to occur in approximately 1,500 individuals in (southern) Holland and Belgium. Perhaps most important of the origin of the disease is whether or not anything can be done about it. Van Wijk: “This condition has two characteristics that are favorable for the development of treatment. First, it is a genetic condition that does not appear until after a few decades of life. If an effective treatment is available for this disease, there is a time frame large enough to apply it before hearing loss really occurs.”
Turn off mutated genes
The other point – developing an effective treatment – is a bit more complicated, but it does offer good starting points. Van Wijk: “The idea is that by specifically turning off the transcription of the transgenic, you can prevent deafness. Without this mutated gene copy, a mutated protein would not be produced and protein clumping would not occur anymore. In addition, it results in one healthy gene copy. Enough protein to maintain good hearing. “
De Vrieze and Van Wijk developed this idea. They and colleagues have now published the results of the research in the scientific journal Molecular Therapy – Nucleic Acids. “The genes in our DNA provide the genetic code for the process of translating into proteins,” says de Vriesi. “To go from gene to protein, you always need a translation process via something called messenger RNA. This is exactly the process that we focused on. The unique DNA error in the DFNA9 gene is also reflected in the RNA. We have developed a small piece of RNA ( RNA) that specifically binds to messenger RNA derived from the mutated DFNA9 gene. As a result, the entire mutated messenger RNA is targeted for degradation. In this way, an essential link is lost and the mutated DFNA9 protein is no longer or is hardly produced. RNA that we affix to the mutant DFNA9 messenger RNA is named antisense oligonucleotide or “genetic patch”.
Point of view!
In recent years, De Vrieze and Van Wijk not only developed this gene patch but also investigated its effect on cultured cells. Their current article mainly describes these results, as the approach works in cultured cells. So, there is a “proof of concept,” as it is called in science. In summary, the research shows that this approach works at the cellular level.
Arthur Robesum of DFNA9 said he was pleased with the study. This provides a real perspective for the approximately 1,500 people in the Netherlands and Belgium who suffer from the condition. The Foundation is also closely involved in this research. Robbesom: “Now it is important to take the following necessary steps in the search as quickly as possible. We will support you wholeheartedly.”
Peter Le Mans
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