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Cystic fibrosis is the most common life-threatening inherited disease in Europe with an estimated 35 000 sufferers. The disease remains, for now, incurable and severely compromises both life span and quality of life.
However, a new era of drug development is on the horizon with the emergence of drugs that are targeting the basic defect in the cells of people with cystic fibrosis. Such promising treatments may be a life-changer for many, but could bypass those with rare genetic mutations of the disease.
The situation arises due to the high cost of clinical trials, which therefore tend to only focus on patients with the most common mutations. Recent advances in personalised medicine approaches based on the use of stem cells may present a promising new avenue of investigation.
The EU-funded HIT-CF project, launched in January 2018, brings together researchers, doctors, pharmaceutical companies and patient representatives with the aim of identifying possible new drugs and new drug combinations using a new approach to testing these.
By taking small samples of rectal tissue from patients, researchers are able to grow ‘mini-intestines’, or organoids, in a culture dish. Because these organoids are made from the stem cells of the patient, they contain the same mutations as the donor and can therefore be used to reliably test responses to novel drugs or new drug combinations, says project coordinator Kors Van der Ent of the Utrecht University Medical Centre in The Netherlands.
“We are pioneering a new approach to the validation and approval of current and future ‘off-label’ treatments for people with rare forms of cystic fibrosis by effectively shifting therapeutic trials from patients to the laboratory,” he explains.
Expanding options for orphan diseases
In the first stage, the HIT-CF project will recruit and take biopsies from 500 patients with rare mutations throughout Europe and use them to grow individualised organoids on which to test responsiveness to several drug candidates.
In a second phase, patients whose organoids respond best to a certain experimental drug will be invited to participate in a clinical trial during which a drug will be administered to the patient directly.
“Our aim is to prove that there is indeed a good correlation between the lab results and clinical trial results,” says Van der Ent. “We will collaborate with the European Medicines Agency to ensure that we have a validated biomarker for testing these patients and hope to acquire enough data to convince them to approve drugs for the European market on this basis.”
Finding new treatment options for cystic fibrosis patients with rare mutations will not only help improve the quality of life of patients and their families, but could also significantly decrease the financial burden of their treatment. It is also expected that this methodology can eventually be extended to other rare genetic diseases, thus impacting the entire field of orphan diseases and offering new hope to many.
The project will also address the issue of biobanking patient samples in Europe, which raises a number of ethical concerns and remains a highly fragmented area with regard to regulation. Questions raised by the use of biological material for research include who has ownership of them, who has access to them and for what purposes.