15 February 2019

Important step towards personalised drugs for cystic fibrosis

Mini-organs predict the effect of drugs on cystic fibrosis

Utrecht researchers have demonstrated that a mini-organ grown outside the body can be used to predict the effectiveness of drugs at an individual level. This is evident from their new study of patients with cystic fibrosis and opens the door to cheaper and more effective drugs for individual patients. The results were published in Cell Reports this week.

Using stem cells, it is possible to grow so-called organoids – mini-organs developed in the laboratory. One of the potential benefits of these organoids is that you can test drugs on them without burdening the patient. These organoids can tell doctors which drugs will work with which patient and which won’t, making it possible to develop personalised drugs.

For the first time, this study demonstrates how reliable such predictions can be for individual patients

‘We had previously described in case studies of two patients that an organoid could be used to prescribe drugs. However, the expansion in this study demonstrates that these results can truly be repeated in a larger study and, for the first time, demonstrates just how reliable such predictions can be for individual patients,’ says researcher Jeffrey Beekman (University Medical Center Utrecht) who led the study together with Kors van der Ent (paediatric pulmonary specialist).

The researchers, who are associated with the Hubrecht Institute and UMC Utrecht (among other institutions) and some of whom work for Regenerative Medicine Utrecht, investigated 36 treatments in 24 patients with cystic fibrosis. Personalised drugs for these patients would be very welcome, as this disease has relatively high numbers of rare genetic mutations. As a result, numerous patients fall outside the scope of many other clinical studies and often do not have access to existing and potentially life-saving drugs as a result.

Intestinal tissue

The efficacy of three different drugs was studied in 24 patients with various different forms of cystic fibrosis. The effects of drugs on the respiratory function and sweat function in patients could be clearly linked to the effects of the medication in the intestinal organoids. These mini-organs were grown from tiny pieces of the patients’ intestinal tissue.

‘As stem cells are stored in a biobank, we can link future and existing drugs to the individual patient in the laboratory ’

Some of the patients with rare forms of cystic fibrosis were also prescribed personal treatment on the basis of drugs available for more common forms of cystic fibrosis. This personalised organoid test was found to be ‘good to excellent’ in terms of its correspondence with the short-term effect of the drug on the patient.

Follow-up study with 500 patients

‘This is the first time we have measured the predictive value of stem cells for individual treatments,’ says Kors van der Ent, paediatric pulmonary specialist at UMC Utrecht. ‘As the stem cells are stored in a biobank, we can link future and existing drugs to the individual patient in the laboratory. Currently, UMC Utrecht is leading a major European study in which we will investigate this further for 500 patients with the rarest forms of cystic fibrosis.’