There has been nationwide newborn screening in Germany since 2016. Since then, every newborn has been tested for a genetic change that leads to cystic fibrosis. Before drugs came along, the conversations that Krystina Poplawska had to have with the parents of affected newborns were often frustrating: she had to explain to them that anything you do could only slow the progression of the disease. “If the child has the F508del mutation, we can now tell the parents that life expectancy and quality of life have improved enormously,” says Krystina Poplawska.
However, it is not yet possible to say by how many years life expectancy will increase. Because the drugs in the combination have only been approved since 2020, there are still no long-term studies on their effect. But according to Marcus Mall, there are already some indications that the life expectancy of those affected, especially if treatment starts early, from the previous average of 57 years, could in future almost reach that of the general population, which is currently 78.5 years for men and 83.4 years for women lies.
“Presumably, the therapy should ideally start even earlier, since chronic lung damage can already begin in preschool age.”Marcus Mall, Charité – University Medicine Berlin
Because cystic fibrosis not only causes acute problems, but also the defective chloride channels also cause medium- and long-term damage and slowly impair the lung tissue, among other things, it should also play a role in life expectancy when the patients receive the new therapy. »Even those affected in their late 40s still benefit significantly from the combination therapy. But the greatest and most lasting effect is probably achieved when children receive the combination therapy at a young age,” says Marcus Mall. While the drug combination was initially only approved from the age of twelve, this age has now been reduced to six years. “Presumably, the therapy should ideally start even earlier, since chronic lung damage can already begin in preschool age,” says Mall. The clinical studies in this age group are currently being carried out.
Another breakthrough in cystic fibrosis in sight?
Also, a major benefit of the drugs is that they correct the chloride channels throughout the body. In contrast to this, with the previous symptomatic therapy, only the respective complaints could be treated in isolation: the accumulation of mucus in the lungs by inhaling expectorant drugs, the indigestion by taking digestive enzymes.
However, not all cystic fibrosis patients benefit from the drug combination. It only works in those patients who have the F508del mutation in the CFTR gene. And one in ten people affected lacks this common mutation. Unfortunately, not much has changed for such cystic fibrosis sufferers: If they take the drug combination, their life expectancy does not increase as much, and their quality of life hardly improves, only due to advances in the treatment of the symptoms. They are waiting for the next revolution in cystic fibrosis therapy, on which researchers around the world are already working diligently. It should even attack one step earlier than the drug combination.
Strictly speaking, the combination of active ingredients is not a direct therapy for the cause: the faulty chloride channels lead to the symptoms, yes, but the fact that they are faulty at all is due to the genes. This is exactly where we want to start with future gene therapies. In recent years, there have been tremendous advances in methods and agents that can be used to induce changes at the genetic level, including CRISPR-Cas9 gene editing and mRNA technology, which became popular with the vaccination against Covid-19. “There are actually a number of promising approaches here, but there are still a few obstacles,” says Krystina Poplawska from Mainz. The ten percent of those affected who do not have the F508del mutation should benefit first and foremost from successes in this area: it would be an opportunity for them to benefit from another revolution in the field of cystic fibrosis therapy.