
Berlin, 07.07.2023
The mucus in the respiratory tract is less viscous, the inflammation in the lungs decreases significantly: These positive and long-lasting effects can be achieved by a triple therapy in patients with cystic fibrosis. Researchers at the Charité – Universitätsmedizin Berlin and the Max Delbrück Center have now documented this in the European Respiratory Journal*. According to the study, the medication alleviates the lung disease in many patients.
Two years ago, a research group led by the Charité showed that the combination therapy with the three active substances elexacaftor, tezacaftor and ivacaftor is effective for a large number of patients with the hereditary disease cystic fibrosis, i.e. it noticeably improves lung function and quality of life. Now, for the first time, the team led by Prof. Dr. Marcus Mall, the former and current head of the study, has investigated the extent to which this therapy also helps in the long term, i.e. over at least twelve months. For this purpose, the researchers took a closer look at the sputum, the secretion of the respiratory tract. “In patients with cystic fibrosis, the mucus in the airways is very tough because it contains too little water and the mucus-forming molecules, the so-called mucins, are too chemically stuck together. The resulting tough mucus clogs the airways, making breathing difficult and leading to chronic bacterial infection and inflammation of the lungs in those affected,” explains Prof. Mall, Director of the Clinic for Paediatrics with a focus on pneumology, immunology and intensive care medicine and of the Christiane Herzog Cystic Fibrosis Centre at Charité.
In the current study, the scientists show that the triple therapy with elexacaftor, tezacaftor and ivacaftor in patients with cystic fibrosis ensures that the respiratory secretion is less viscous and the inflammation and bacterial infection in the lungs decrease. “And this happened over the entire duration of the study, which was one year. This is so significant because earlier medications had again led to an increase in the bacterial load in the airways,” explains Dr. Simon Gräber, also from the Clinic for Paediatrics with a focus on pneumology, immunology and intensive care medicine at the Charité and co-leader of the study. Seventy-nine adolescents and adults with cystic fibrosis and chronic lung disease took part in the study.
Success for the treatment of cystic fibrosis, further research important
“This is a great success for the treatment of cystic fibrosis,” says Prof Mall. “Nevertheless, we cannot yet speak of a normalisation or even a cure for the patients. Chronic lung changes that have developed over many years of the disease unfortunately cannot be reversed.” For those affected with advanced lung disease, established treatment approaches with inhalations of mucolytic drugs and antibiotics as well as physiotherapy therefore remain important.
“We will continue to conduct intensive research into how therapies that attack cystic fibrosis via the disease-causing molecular defects – such as the triple medication now being studied – can become even more effective. This includes in particular an early start of therapy in infancy with the aim of preventing chronic lung changes as far as possible,” reports Prof. Mall. “In addition, this therapy is currently not available for about ten percent of our patients due to their genetic conditions,” adds Dr. Gräber. “That’s why we are also working hard on new molecular therapy approaches to be able to effectively treat all people with cystic fibrosis.
In addition, the scientists are working to better understand the malfunction of the mucus in cystic fibrosis and to develop new mucolytic agents. This could then also benefit patients with common chronic inflammatory lung diseases such as asthma or COPD.
*Schaupp et al. Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor on Sputum Viscoelastic Properties, Airway Infection and Inflammation in Patients with Cystic Fibrosis. European Respiratory Journal (2023). doi: 10.1183/13993003.02153-2022
Cystic Fibrosis
Cystic fibrosis is one of the most common fatal hereditary diseases worldwide. In Germany, up to 8,000 children, adolescents and adults are affected. Due to a disturbance of the salt and water balance in the body, a viscous secretion forms in cystic fibrosis sufferers, which damages organs such as the lungs and the pancreas. This leads to a progressive loss of lung function and shortness of breath, which still significantly reduces life expectancy despite improved treatment approaches. Every year, about 150 to 200 children are born with the rare disease in Germany.
About the triple therapy
Since August 2020, a combination of the three active substances elexacaftor, tezacaftor and ivacaftor has been available in Europe, which noticeably improves the lung function and quality of life of patients with the most common genetic defect F508del. This means that the therapy is suitable for almost 90 percent of cystic fibrosis patients. Since the beginning of 2022, the triple therapy can already be used in children from the age of six.
About the study
The study was carried out in cooperation with scientists from the Max Delbrück Center and within the framework of the Collaborative Research Centre “Dynamic Hydrogels at Biointerfaces” (SFB 1449). Prof. Mall is the deputy spokesperson of this SFB. He is also an Einstein Professor and heads cystic fibrosis research at the German Centre for Lung Research (DZL).
Picture: The triple therapy with the active ingredients elexacaftor, tezacaftor and ivacaftor ensures that the airway mucus in cystic fibrosis (green in the picture above) is less tough. This makes it easier to remove bacteria from the lungs and reduces airway inflammation cells. © Charité | Laura Schaupp