Yesterday the U.K. press was full of the news that a gene therapy trial to treat cystic fibrosis is on hold after the sponsor ran out of money. Although the study's approach wasn't a sure bet, the researchers hoped to go further than any other gene therapy trial yet for this relatively common inherited disease that fills people's lungs with sticky mucus that promotes deadly infections.
Cystic fibrosis (CF) is caused by a defect in the CFTR gene, which codes for a protein that carries chloride ions across the cell membrane. In the 1990s, researchers tried using a virus or fat particles to insert the correct CFTR gene into patients' lung cells. But these approaches didn't work very well and, in the case of viral vectors, raised concerns about a possible dangerous immune response. The current U.K. trial is again using fats, or lipids, but the DNA includes a segment called a promoter that should make gene expression last longer, says Eric Alton of Imperial College London, who heads the UK Cystic Fibrosis Gene Therapy Consortium.
His team is winding up a safety study in which 40 patients breathed in a single dose of a lipid-CFTR DNA mixture. To see if the new DNA was working, the researchers then inserted an electrical device into the patients' nose or lungs that measured ion transport by CTFR proteins (see early results here). There were "some very exciting changes with some of the patients," Alton says: some had improved CTFR function and several even had normal levels for up to 2 months. However, the study didn't look for clinical benefit, Alton says.
But plans to do just that starting this summer in a 1-year, multidose study with more than 100 patients, some of whom would get a placebo, are now on hold. Alton says that the UK Cystic Fibrosis Trust, which had poured £30 million into the research so far, told his team in late February that because donations are down, the charity can't fund the new trial. (Today the team received an industry-sponsored Medical Futures Innovation Award to use a lentivirus to deliver the CTFR DNA, but the approach won't be ready to test in patients until 2014 or 2015, Alton says.)
The Cystic Fibrosis Trust is asking donors for £6 million by October so that the trial can proceed next spring. Even that amount is "absolutely the bare minimum," Alton says. Researchers will take cost-saving steps such as freezing some blood samples instead of analyzing them right away, says Alton, who is already laying off some of the consortium's 70-some staff members.
Other researchers have been "a bit skeptical" about using lipids to deliver a gene to the lung because the approach isn't very efficient compared with viruses, says Richard Boucher of University of North Carolina, Chapel Hill. On the other hand, he says, lipids may be safer. "It is a tough calculus, but gene therapy for CF lung disease is still a realistic possibility and studies should be encouraged--especially well-done ones like the U.K. trial. Sorry to hear they are low on funds," Boucher says.