The new Cystic fibrosis transmembrane conductance regulator (CFTR) modulators hold great promise as targeted therapies (for both children and adults with CF) as they are designed to correct the function of the defective protein made by the CF gene. Unfortunately, different CF mutations cause different defects in the protein and there are ~1800 different CF mutations. The therapies that have been developed so far are effective only in people with specific mutations (many patients will not be approved for treatment based on the majority of mutations being excluded from the CFTR modulator clinical trials). Therefore, the solution to this problem is a personalised CFTR functional screening test to determine the likelihood of whether a patient with a given CF mutation will respond to a given drug. There are currently two CFTR modulators approved in the US and multiple European countries: Ivacaftor (Kalydeco®) and Lumacaftor/Ivacaftor (Okrambi®), however the latter has not been approved in Australia. Although there are many more CFTR modulators (12 drugs undergoing trials) showing promise in current clinical trials, unfortunately they will never be trialled for every CF mutation and so many CF patients will miss out. The development of our pre-treatment CFTR functional screening test could have two major benefits:
- It will match the right patient to the correct drug and hence enable patients to receive the most optimal therapy faster while saving healthcare costs.
- In the future this test may enable some patients with other CF mutations, which were not included in the clinical trials, to receive these new therapies.
Our aim is to use the CFTR functional screening test we have developed to predict the response of individual Australian CF patients (with any CF mutation) to the new CFTR modulator therapies. This test requires a routine biopsy to be taken from each patient, grown in the laboratory with a new stem cell technology, and then tested to determine response to the CFTR modulators.
This project would be a first of its kind precision medicine study for CF in Australia. A similar research project in the Netherlands achieved such rapid success that it led to a mandatory test (as of 2016) for all CF patients prior to receiving therapy with a CFTR modulator. This test is now part of the Netherlands healthcare guidelines to better target therapies for patients with CF. We aim to achieve a similar outcome in Australia.