Stem cells from intestines of cystic fibrosis patients can predict in the laboratory whether or not a specific medicine will be effective.This will enable medical physicians to select the right medicines for optimal treatment of individual patients.Researchers at University Medical Center Utrecht are publishing these results in Science Translational Medicine today.

Some forms of cystic fibrosis (CF) are so rare that the usual clinical studies to test efficacy of medicines cannot be performed because there are too few patients. Therefore, physicians are looking for alternative ways to develop new medicines for these patients. Researchers at UMC Utrecht have now demonstrated in a proof of principle study among a small number of patients that the efficacy of a medicine can be demonstrated for a particular patient using that patient's intestinal stem cells. This enables the physician to select the medicine or combination of medicines that is most likely to be efficacious in that particular patient.

Organoids

Medical biologist Dr. Jeffrey Beekman heads the laboratory that developed the CF test. Beekman: “We are able to grow stem cells into what are known as organoids, in the laboratory. These organoids are genetically identical to the patient and ideal for studying cystic fibrosis. You can tell from them whether the disease will be mild or severe and predict whether or not the patient will respond to certain medicines. This offers new perspectives for applying existing medicines as well as for developing new ones.”

New era

“A number of extremely expensive medicines are currently being marketed. While their eficacy in clinical research is sometimes disappointing, they may be truly life-saving for individual patients,” says prof. dr. Kors van der Ent, head of the CF Center at UMC Utrecht. He continues: “Some of these patients were waiting for lung transplants, but can now be found on the hockey pitch again thanks to the right medication. Their lives have completely changed. With our new organoid technology, which we have already used on some 200 CF patients, we are entering a new era of individualized treatment.

Drs. Jacquelien Noordhoek-van der Staaij is director of the Netherlands Cystic Fibrosis Foundation (NCFS) and of CF-Europe, the umbrella organization for all European organizations for CF patients. She believes this discovery by the Utrecht researchers will be of paramount importance for patients worldwide. “There are many different genetic forms of CF and every patient responds differently. Doctors are struggling with the positioning of new, pioneering medicines, as each patient responds just that little bit differently. The entire field of CF patients and practitioners is welcoming this with open arms. We have been waiting for this all along.”

UMC Utrecht CF Center

The CF Center at UMC Utrecht is the largest CF center in the Netherlands, treating some 500 patients (one third of all patients in the Netherlands). In addition, the center studies the causes and treatment of CF, in close collaboration with the Hubrecht Institute and with support from the NCFS.

For an informative short movie about the use of organoids for drug testing in CF, click here

Reference

Dekkers JF, Berkers G, Kruisselbrink E, et al. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Science Translational Medicine 2016 DOI: 10.1126/scitranslmed.aad8278