Cystic fibrosis (CF) is the most common fatal genetic disease affecting Canadian children and young adults. One in every 3,600 children born in Canada has CF, which occurs when a child inherits two abnormal genes, one from each parent. Approximately, one in 25 Canadians carry an abnormal version of the gene responsible for CF. Carriers do not have CF, nor do they exhibit any of the symptoms of the disease.
Over 4,000 Canadians live with CF, which affects their lungs and digestive system, where the linings of these vital organs become clogged with thick mucus. This can lead to chest infections, persistent cough, wheezing and shortness of breath, bowel disturbances, weight loss or failure to gain weight, salty tasting sweat, infertility in men and decreased fertility in women.
The median age of survival for Canadians with CF was 50.9 years in 2013, over 25 years higher than it was in the early 1980s. However, the complications of ongoing infections and inflammation in the lungs, which eventually lead to loss of lung function, cause death in the majority of people with CF. Other frequent complications include difficulty in digesting fats and proteins and vitamin deficiencies due to loss of pancreatic enzymes.
While there is no cure for CF, remarkable progress in CF research has been made since 1989, when Canadian researchers at the Hospital for Sick Children (SickKids) discovered the gene responsible for CF — CFTR.
“Over the past decade there has been tremendous progress with regard to therapy discovery conducted using generic cells induced to possess a particular CF mutant protein,” Dr. Christine Bear, Senior Scientist and Co-Director of the CF Centre at SickKids, said in a press release. “While this approach led to the discovery of a drug called Kalydeco, we believe that a new discovery strategy is needed during the upcoming 10 years to find the next generation of therapies effective in treating all CF patients.”
Kalydeco is also a very expensive medication, one that is not covered by all provinces in Canada. Also, because of different CFTR mutations and the uniqueness of each patient, Kalydeco is only effective for a small population of those with CF. “While this is a big step for CF, there is still much work to be done,” added Dr Bear.
Stem cells may provide some of the answers Dr. Bear and others are searching for. Cystic Fibrosis Canada, a national charitable not-for-profit corporation established in 1960 to find a cure or control for CF, recently funded Dr. Bear and her team at SickKids for their project, ‘Individualizing cystic fibrosis therapy.’
Dr. Bear’s lab is developing a resource of induced pluripotent stem cells or iPS cells from a cohort of patients with CF to represent the Canadian patient population. Patient-specific iPS cells will then be differentiated into lung epithelium and used to assess, explain and eventually predict individual specific responses to emerging therapies.
The approach, the first of its kind in Canada, will enable the future implementation of techniques to monitor functional correction of CFTR — techniques that are essential for pre-clinical trials comparing patient-specific responses to CF therapies and the identification of the best treatment for each CF patient.
While the work is in the early stages, it does offer hope that new approaches defeating CF can be made available some day soon.