In the past, attempts to find out if gene therapy could work as a treatment for cystic fibrosis have not been met with much success. Now, new research shows how an improved gene therapy showed promising results in mice with cystic fibrosis.
The study, published in the American Journal of Respiratory and Critical Care Medicine, is the work of a European team led by researchers from KU Leuven in Belgium.
The researchers also showed that cell cultures from patients with cystic fibrosis responded well to the new gene therapy.
Cystic fibrosis is a genetic disorder that usually begins in childhood and causes the lungs and digestive system to become clogged with thick, sticky mucus, making breathing difficult. Symptoms include persistent cough, recurring chest and lung infections and poor weight gain.
While there is currently no cure for cystic fibrosis, treatments can alleviate the symptoms and help patients live longer.
Cystic fibrosis arises from a faulty gene called CFTR, which codes for a protein that is important for controlling channels through which chloride and water ions flow out of cells. In people with cystic fibrosis, these ion channels are either absent or do not work properly.
Senior author Zeger Debyser, a professor in molecular virology and gene therapy at KU Leuven, notes that a new drug that repairs faulty ion channels was launched a few years ago. However, it only works in a minority of patients with cystic fibrosis.
Gene therapy is a treatment where a faulty gene underlying a disease is replaced with a healthy copy.
The authors explain in their paper that while clinical trials using various methods of inserting a healthy CFTR gene have proved to be safe and well tolerated in patients with cystic fibrosis, none has “led to a clear and persistent clinical benefit.”
“However,” says Prof. Debyser, “as gene therapy has recently proven successful for disorders such as haemophilia and congenital blindness, we wanted to re-examine its potential for cystic fibrosis.”
The new gene therapy the researchers used is called “recombinant adeno-associated virus-(rAAV)” gene therapy. It employs a relatively innocent AAV virus to insert a healthy copy of CFTR into cells.
The new rAAV gene therapy showed positive results in tests of mice with cystic fibrosis and also cultures of gut cells from patients with cystic fibrosis.
Prof. Debyser explains what happened:
“We administered the rAAV to the mice via their airways. Most of the CF [cystic fibrosis] mice recovered. In the patient-derived cell cultures, chloride and fluid transport were restored.”
While the researchers are cheered by these results, they point out there is still a long way to go before such an approach is ready for use in cystic fibrosis patients, and they add that it would be wrong to raise hopes at this stage.
Prof. Debyser says, for example, they still have to examine how long the therapy works for. Will repeat doses be required? He concludes on an optimistic note:
“But gene therapy clearly is a promising candidate for further research towards a cure for cystic fibrosis.”
Earlier this year, Medical News Today learned how researchers who used yeast to study the root cause of cystic fibrosis found that a small molecule can take the place of a missing protein in yeast cells with faulty ion channels, enabling them to work again.