Yellow fluorescent beads are embedded in mucus spinning on top of cultured lung cells in the laboratory to reveal how freely it is moving.
Credit: Raymond J. Pickles
SYDNEY: A new gene therapy treatment for cystic fibrosis may offer a more efficient way to deliver a corrected gene into the lungs of sufferers of the inherited disorder.
Gene therapy has long been envisioned as a treatment strategy for cystic fibrosis (CF), but problems with the technique have stymied these efforts. Now, in a study reported in the latest PLoS Biology, scientists report that it may be possible to use an inactivated version of the parainfluenza virus (PIV), which infects lung tissue and causes common colds.
Limitations of gene therapy
“Getting the gene into the right cells and getting into enough of the cells to reverse the CF phenotype is the breakthrough,” said Raymond Pickles of the Cystic Fibrosis Research and Treatment Centre of the University of North Carolina in Chapel Hill, USA.
“The difficulty with gene therapy is that the ways we have tried [in previous studies] to introduce the gene into the lung just don’t work well enough. We have engineered a virus that can do this job well but it has its own limitations,” he said.
Cystic fibrosis results from a mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which produces a protein involved in the transport of chloride ions across cell membranes.
The lack of this protein leads to thickened mucus in the lungs and a decreased ability to clear it away. As a result, bacterial infections can take root and long-term inflammation destroys the airways and eventually causes a fatal decline in lung function.
"Simple disease with complex consequences"
“It’s a simple disease with complex consequences, such as increased susceptibility to bacterial infection,” said Pickles.
“We have focussed on correcting the genetic defect to halt the disease before infections and tissue damage take place. It’s always harder to reverse tissue damage than to try to stop it happening in the first place.”
In their new study, researchers led by Pickles used PIV as a vector to deliver the corrected gene to human lung cells that are collected from patients and cultured in the laboratory in a model that is meant to represent the lung.
“We decided that we had to learn from nature and if these kinds of viruses [PIV] had evolved to infect the lung… we needed to use that property for our own devices,” he said.
