Hereditary deafness can manifest itself in different ways. Often the hereditary error (mutation) immediately causes deafness from birth. Sometimes, as with DFNA9, you only become deaf after forty, fifty, sixty years. That has everything to do with the way DFNA9 is put together. Every human gets half of his genes from his father and mother and has both a DFNA9 gene from his father and mother. If you have two healthy copies of the DFNA9 gene, then nothing is wrong. If you receive a mutated copy of the gene from your father or mother, deafness will develop later in life.
Erik de Vrieze and Erwin van Wijk, both researchers at Hearing & Genes in the Ear, Nose and Throat Department, have conducted extensive research into the condition. De Vrieze: “We now know that you actually produce enough of the associated DFNA9 protein with just one good gene copy to be able to hear well for life. But there is a catch with this condition. The mutated protein is, in a way, bothering the good protein. It sticks to it, so that the good protein can no longer do its job. This clumped protein spaghetti is constantly being cleaned up, but after decades the clean-up service in the hearing cells is reaching its limit. It went well for a long time, but suddenly a tipping point arises, a threshold value is exceeded. The waste accumulates, the hearing cells start to function worse and die over time. After years of good hearing, DFNA9 patients suddenly notice that their hearing is deteriorating, sometimes deteriorating very quickly. Until at some point they will become deaf. ”
Enough time for treatment
The DFNA9 mutation seems to have arisen for the first time in someone in the Southern Netherlands, somewhere at the end of the Middle Ages. This can more or less be deduced from the spread of the fairly unique clinical picture, which is now estimated to occur in about 1,500 people in the (southern) Netherlands and Belgium. Perhaps even more important than the origin of the disease is whether anything can be done about it. Van Wijk: “This condition has two favorable characteristics for seeking treatment. Firstly, it is a hereditary condition that only manifests itself after a few decades. If you have treatment for the disease, then there is sufficient time available to apply it before the hearing loss really strikes. ”
The other point – developing an effective therapy – is a bit more complicated, but offers good starting points. Van Wijk: “The idea is that by specifically turning off the mutated gene copy you can prevent deafness. Without this mutated gene copy, no mutant protein will be produced and clumping will no longer take place. In addition, one healthy gene copy alone produces enough protein to maintain good hearing. ”
De Vrieze and Van Wijk further developed this idea. They and colleagues have now published the research results in the science journal Molecular Therapy – Nucleic Acids. “Genes, recorded in the DNA, form the code for proteins,” says De Vrieze. “To get from a gene to a protein, you always need a translation process via so-called messenger RNA. And that is exactly what we focused on. The unique DNA error in the DFNA9 gene is also reflected in the RNA translation. We made a piece of RNA that fits exactly on that. And that also immediately signals that the entire messenger RNA must be cleaned up. In this way, an essential link is lost and the wrong protein is not or hardly produced anymore. We call the piece of RNA that we stick on the wrong messenger RNA an antisense oligonucleotide, also called ‘genetic patch’. ”
In recent years, De Vrieze and Vanwijk have not only made this genetic patch, but also investigated its effect in cultured cells. Their article is now mainly about that. Because the approach works in those cells. So there is a ‘proof of concept’, as it is called in science. In short, the research shows that the approach works at the cellular level.
Arthur Robbesom of the Foundation ‘The ninth of …’ is delighted with the research. “This offers a real perspective for some 1,500 people in the Netherlands and Belgium who have the condition.” The foundation is also closely involved in the research. Something we will wholeheartedly support. ”
A genetic patch to prevent hereditary deafness
Source link A genetic patch to prevent hereditary deafness