The underlying genetic defect responsible for cystic fibrosis may be treated by an experimental oral drug called PTC124, researchers have revealed.
Sponsored by PTC Therapeutics (PTC), the study showed that the drug can induce the production of functional cystic fibrosis transmembrane conductance regulator (CFTR) protein-required for normal function of the lung, pancreas, liver, and other organs-in patients with nonsense-mutation cystic fibrosis (CF) who generally do not make this protein.
Researchers from the Hadassah Hebrew University Hospital in Jerusalem enrolled 23 adult patients with nonsense-mutation CF - median age 25 years - for the study.
More than 90 percent of patients had severe CF with compromised lung function, pulmonary infection with Pseudomonas or other pathogenic bacteria, and pancreatic insufficiency.
The subjects were assessed in two 14-day treatment courses of oral PTC124 therapy, the first given at a lower dose and the second given at a higher dose.
The researchers found that at both dose levels, treatment with PTC124 was associated with statistically significant improvements in CFTR-mediated chloride transport with over half of the patients entering the normal range during at least one treatment course.
The drug induced chloride transport responses and normalization of CFTR activity across the variety of patient genotypes tested.
According to the researchers, the drug was generally well tolerated, and all patients had 90 per cent treatment compliance.
"This study demonstrates the potential for personalized medicine, combining selection of patients with a specific type of genetic mutation and a drug treatment that has been specifically designed to overcome that mutation," said Dr. Eitan Kerem, head of pediatrics and the CF center at the Hadassah University Hospital in Mount Scopus, Jerusalem and the lead author of the study.
Dr. Preston Campbell, III, Executive Vice President of Medical Affairs at the Cystic Fibrosis Foundation, said: "We are very pleased by this positive outcome from our ongoing collaboration with PTC. The development of PTC124 fits well with our strategic goal of supporting approaches that have the potential to modify the course of CF. We are continuing to work together with PTC and the broader CF medical community to support the next steps in the evaluation of PTC124 for the clinical benefit for the treatment of nonsense-mutation CF."
Dr. Stuart W. Peltz, President and Chief Executive Officer of PTC Therapeutics, said: "Based on these results, we intend to initiate a Phase 2b study later this year to evaluate the clinical benefit of PTC124 in adults and children with nonsense-mutation-mediated CF. Given the potential applicability of PTC124 to multiple genetic disorders, we have a pivotal study of PTC124 for nonsense-mutation Duchenne/Becker muscular dystrophy ongoing and are planning proof-of-concept studies in additional genetic disorders."
A research article on the findings has been published in the Lancet.