New target for cystic fibrosis drug development: Ceramides
Cystic fibrosis (CF) is a deadly respiratory disease characterized by thick mucus in the lungs. This mucus becomes colonized by pathogens and initiates a vicious cycle of infection and inflammation. Although no effective therapeutic options for CF exist, Danuta Radzioch, PhD (Infectious Diseases and Immunity in Global Health Program), and her research team have made important advances with the help of industry.
Did you know? It takes 12 to 15 years and around $1 billion to bring a new drug from discovery in the lab to the marketplace.
The team discovered that ceramides—a specialized type of lipids found in human cells—are imbalanced in the lungs of CF patients. Ceramides are involved in triggering immune responses necessary to combat infections. Thus, severely imbalanced ceramide levels are associated with an inability to mount an effective immune response against these pathogens. The team further demonstrated that administration of the drug fenretinide can restore normal levels of protective ceramides in CF patients.
“CF patients are often treated with corticosteroids, but these drugs suppress the immune system and impede its ability to fight infection,” explains Danuta Radzioch. “What makes fenretinide so exciting is that, in contrast to corticosteroids, correcting ceramide imbalance actually improves the ability of the immune system to combat pathogens.”
These groundbreaking findings from the Phase Ib trial were published in the Journal of Molecular Medicine, and Laurent Pharmaceuticals Inc. is sponsoring a Phase II clinical trial.
The development of fenretinide for the treatment of CF depended on dedicated collaborators, says Danuta Radzioch, including Drs. Elias Matouk and Larry Lands (Translational Research in Respiratory Diseases Program), the McGill Office of Technology Transfer, industry partners, and Costas Karatzas, PhD, Director of the Business Development Office at the Research Institute of the McGill University Health Centre. “This ongoing team effort enabled us to protect critical patents, secure funding opportunities and partner with a private company so that our research could transition through pre-clinical and early clinical trials, with the ultimate goal of benefitting CF patients,” she explains.
