A urine sample may turn out to be enough to find out how well new drugs for patients with cystic fibrosis work. Researchers from Aarhus University have developed this urine test. The results have just been published in the Journal of the American Society of Nephrology and are an international collaboration project with the University of Regensburg/Germany.
2020.08.13 |
Cystic fibrosis is one of the most common hereditary, deadly disease in the western world, and in Denmark approximately fifteen children are born with cystic fibrosis every year. When the disease was first classified, average life expectancy was five years. Today, half of cystic fibrosis patients live more than 42 years thanks to extensive supportive treatments and close expert patient follow up.
Professor Jens Leipziger from Aarhus University and his group are the researchers behind a new research finding, which can be used to assess the effect of a new medicine for patients with cystic fibrosis. They explain that cystic fibrosis is a disease caused by mutations in the epithelial chloride channel, called CFTR. Healthy people form natural CFTR, while for patients with cystic fibrosis, this either does not function or functions incorrectly.
In the lungs and the intestines, the defect means that mucus has an abnormally tough and sticky consistency. The tough mucus causes problems in the airways in particular, which in turn creates good growth conditions for harmful bacterial infections. These may start an inflammatory reaction in the lungs that destroys the lung tissue and in time leads to loss of lung function.
"The new medications can increase the function of the CFTR channel even if this is defective. Our results open for the development of a urine test for cystic fibrosis patients, which we want to utilise to see how effective the treatment is,” he says.
“The test uses the kidney's ability to secrete base in patients. And because the new treatments aim to improve the functioning of CFTR, this is actually a possible target for measuring whether a treatment is effective,” explains Jens Leipziger.
The study has examined mice and patients with cystic fibrosis and shown that CFTR is essential for the ability of the kidneys to secrete base with the urine.
The researchers discovered that both patients and mice with cystic fibrosis have a markedly reduced ability to increase their base secretion with urine, and this led the researchers to the idea of using the ability to increase base excretion in the urine.
"In our study we’ve established a drinking test with bicarbonate enriched water. Bicarbonate is a weak base, and the same as you find in baking powder. We’ve subsequently observed that the ability to increase the base content of the urine increased in a pilot group of CF patients who were treated with medicines that activated CFTR," explains Jens Leipziger.
The research team’s goal is now to develop the urine test so that it can be used among cystic fibrosis patients, and a larger clinical study to investigate this among Danish cystic fibrosis patients has just begun.
Professor and AIAS JCS Fellow Jens Leipziger
Aarhus University, Department of Biomedicine
Tel.: (+45) 6020 2760
Email: leip@biomed.au.dk