In short
- At the moment, patients with genetic hearing damage are forced to rely on hearing aids or cochlear implants. This means that their hearing will never fully recover.
- Gene therapy is changing this. Dorien Verdoodt investigates how people with the hereditary disease DFNA9, which leads to balance and hearing loss, can be preventively treated with an injection that removes the defected piece of DNA in their inner ears.
An injection to prevent bad hearing? It almost sounds like science fiction, but for at least one specific condition it’s increasingly becoming a reality. We talked to Doctor of Medical Sciences Dorien Verdoodt about her research into a brand-new treatment for genetic balance and hearing loss.
“Cutting away” bad pieces of DNA
At the Resonant Labs research group of UAntwerp, Dorien Verdoodt and Vincent Van Rompaey are looking for solutions for patients with DFNA9. ‘DFNA9 stands for Deafness Autosomal Dominant 9,’ Verdoodt explains. ‘It’s a hereditary disease that leads to balance and hearing loss. As opposed to, say, hearing damage after being exposed to loud music, the damage is genetic in the case of DFNA9. Patients inherit an inner-ear gene mutation from their parents, which leads to balance and hearing loss from the age of thirty. What’s more, the disease is progressive: the symptoms get worse and worse, culminating in complete deafness.’
We inject a specific protein into the patient’s inner ear. This protein finds the mutated piece of DNA and cuts it away, as it were.
At the moment, these patients are forced to rely on hearing aids or cochlear implants. ‘But those will never bring the hearing back to the original level,’ says Verdoodt. ‘And they’re also not ideal for certain sound signals, such as music. For balance loss there isn’t even a solution in the market yet.’
This is why, together with colleagues from UAntwerp and Radboud University Nijmegen (the Netherlands), she is developing a method to preserve original hearing and balance. ‘The idea is to inject a specific protein into the patient’s inner ear. This protein finds the mutated piece of DNA and cuts it away, as it were. The cut is automatically repaired by the body.’ It’s important to carry out the treatment preventively, i.e. before the symptoms come to the fore. ‘This is because we don’t know whether the method can reverse balance and hearing loss,’ says Verdoodt. ‘Potential patients can therefore get tested for DFNA9 from the age of 18. As it concerns a hereditary and dominant condition, they can infer from their family tree whether they’re at risk. Their parents can’t be carriers without showing symptoms themselves.’
A brand-new method
With this treatment for genetic balance and hearing loss, Verdoodt has entered highly innovative territory. The underlying CRISPR-Cas technique to cut DNA was only discovered about ten years ago, and was awarded the Nobel Prize for Chemistry in 2020. There are only a few places in the world where CRISPR-Cas is already being used to cut away bad DNA mutations from the inner ear. And in Belgium this is only done at UAntwerp, by Verdoodt’s team!
As the underlying technique is so new, Verdoodt’s research is also still in the laboratory phase. ‘This means we’re not testing on human patients yet. We are, however, already running tests on mice. And the results are promising.’ So, is there still a lot left to do before the method can be used in practice? Verdoodt nods. ‘First, the mice tests must demonstrate whether the technique is safe and effective. After that, we can transition to clinical studies involving humans, which are always done in stages. Only when those results are good, we can carry out the treatment in practice. But that will take at least a few years.’
Hope for patients
One group of people that can’t wait for that moment to arrive are Dutch and Flemish DFNA9 patients, who have united under the flag of De negende van... They follow the research closely. ‘It’s nice to be in contact with them,’ says Verdoodt. ‘It firmly grounds my fundamental research in reality. Besides, it’s not a coincidence I focus on DFNA9: one of the specific gene mutations that leads to the disease is most prevalent globally in Flanders and the southern parts of the Netherlands, with about 1,500 patients. So my target group is really here. And as the condition is genetic, these people aren’t only waiting for a remedy for themselves, but also for their children and grandchildren.’
Verdoodt concludes by looking beyond DFNA9, because other patients can also be helped with this technique. ‘Cutting away bad pieces of DNA can also be applied to other genetic diseases, particularly when they manifest themselves at a later age and preventive intervention is possible. The injection does not to be adjusted to the genetic error. Another protein must be identified, for instance.’
In any case, it’s certain that the CRISPR-Cas technology is nothing short of a revolution in the treatment of genetic diseases and provides hope to a large group of patients!
Deafness and dementia
Did you know that hearing loss is the main risk factor for dementia that you can influence yourself? Scientists from UAntwerp and VUB tell all about it in Nieuwsblad.
Test yourself and discover how your brain can remain fit!