Boost the efficacy of gene therapy for Cystic Fibrosis
Gene therapy could mean a permanent cure for all people with cystic fibrosis (PwCF), but does not yet live up to this promise due to lack in efficiency. In this public-private partnership, Ewart Kuijk and Zhiyong Lei from the UMC Utrecht aim to determine if drugs from FAIR therapeutics can boost the efficacy of gene therapies for cystic fibrosis.
Cystic fibrosis (CF) is caused by mutations in the CFTR gene leading to thick mucus and damage to the lungs and other organs resulting in high morbidity and mortality. Novel medicine, called CFTR modulators, can restore CFTR function in a subset of PwCF. However, CFTR modulators are expensive, costing €194.040 per patient per year amounting to a total cost of €156 million per year in the Netherlands. In addition, an estimated 20% of PwCF do not respond to these drugs.
All PwCF, including those who currently do not benefit from CFTR modulators, could benefit from gene therapy, but delivery of such therapies to the airway epithelium remains challenging and has thus far not resulted in improved clinical outcome. Here, we use lab-grown miniature lungs, also known as organoids, derived from PwCF to determine if the modulators from FAIR therapeutics, a cheap alternative to the modulators currently on the market, can synergize with gene therapies to overcome the genetic defect that causes CF. This could accelerate gene therapy development and provide all PwCF the prospect to lead long and fulfilling lives.
We pursue the following deliverables:
- Create gene therapy particles to restore CFTR function in lung organoids.
- Determine dose response curves for these gene therapy particles
- Determine synergy between CFTR modulators from FAIR therapeutics and gene therapy particles
