UAB researchers are testing drugs that fix or bypass the “broken” genes that cause cystic fibrosis, says John Paul Clancy, M.D., pulmonary professor of pediatrics and one of more than 50 researchers in UAB’s Gregory Fleming James Cystic Fibrosis Research Center.
“We’re in a very exciting period in CF research,” Clancy says. “Historically, we treat the symptoms. But there are drugs in development that restore function to the genes that cause CF. These drugs try to make the broken genes work and many of the drugs that work in pre-clinical models are entering phase II studies in CF patients.”
In fact, Clancy met with Food and Drug Administration representatives April 23 to discuss the success of PTC124, a drug that has demonstrated that it restores the function of CF gene mutations caused by nonsense mutations.
“It essentially restores the function to one of the classes of mutant CF genes,” Clancy says.
“This line of work grew directly out of research started at UAB under the direction of David Bedwell, Ph.D., professor of microbiology.”
UAB researchers also have been playing a major role in the development of a second class of drugs that target another mutation in the gene that causes CF; the pre-clinical research also shows the drugs work. Phase II studies at UAB testing these Vertex agents are to begin the first week of May.
“When you have CF genes that don’t work, salt doesn’t move right in various organs,” Clancy explains.
“One way to fix that is to make the genes work again. Another way is to go around the problem by using other salt transport pathways in the cells. If you’re able to go around it, hopefully it will help patients get by without having to use the broken gene. It creates a backup pathway.”
UAB also is participating in a Phase III study sponsored by Inspire Pharmaceuticals, Inc., that tests the ability of an agent to activate a backup salt transport pathway and improve lung function in CF patients.