WASHINGTON -- Every day for a week, Dannon Baker swallowed a little white pill as part of an experiment to see if a new type of therapy will finally attack the cause of deadly cystic fibrosis rather than just treat its symptoms.
Studies of three drugs called "gene assist therapies" are in their early stages, experts caution. But, if they work, Baker and other patients could expect more normal lives by using a daily medicine to control a genetic defect that causes cystic fibrosis.
"This is a great time," says Dr. Pamela Zeitlin of Johns Hopkins University, which is testing two of the gene-assist drugs. "None of these drugs are cures -- they would have to be continually taken. But it's a very good idea."
That promise led the 24-year-old Baker to volunteer for the study of one drug candidate, a relative of caffeine called CPX.
"Obviously, taking a medicine for a week isn't going to change my life," said the Atlanta woman, who, like the scientists, will not learn the study's results until fall. "But down the road, it might."
Cystic fibrosis afflicts about 30,000 American children and young adults. The disease attacks patients' lungs with a thick mucus and most die from lung damage or infection. CF also harms digestion and vitamin absorption by clogging other organs, and causes patients to excrete high levels of salt through sweat.
Treatments to fight lung infections and improve nutrition have improved care dramatically. But they treat only symptoms.
In the majority of patients, CF's damage stems from a single genetic defect: It skews a protein called CFTR that is responsible for balancing the salt content of cells lining the lungs and certain other organs.
CFTR is supposed to travel to a cell's surface to create openings, or channels, for chloride ions to exit the cell. But if CFTR is mutated, it dies before ever reaching the surface, so chloride cannot escape. The chloride then mixes with sodium inside cells and a resulting salt buildup prompts the dangerous mucus formation.
Gene-assist drugs would circumvent this, not by curing the genetic defect but by helping the mutated protein work more normally.
CPX, the candidate furthest in testing, "provides eyeglasses and a cane to help (the mutated protein) find its way through the cell and do its work," said Dr. Harvey Pollard, who discovered the drug while at the National Institutes of Health. Although the drug is related to caffeine, caffeine itself does not help cystic fibrosis, he said.
The drug binds to mutated CFTR and chaperones it to the cell surface. Once there, even defective CFTR can shuttle out a little chloride. But CPX also boosts the protein's power to open chloride channels. That double whammy excites the Cystic Fibrosis Foundation, which is helping to fund CPX's development.
"CPX was able to induce a massive secretion of chloride from these CF cells" in test-tube studies, said Pollard. "At that point, we realized we had something really good going."
Now the question is whether the drug works in patients the way it did in Pollard's laboratory.
SciClone Pharmaceuticals, a California biotechnology company, licensed CPX from the government and is sponsoring clinical trials to find out. Test results are expected in several months.
Two other possible gene-assist drugs are in earlier clinical trials:
-- Johns Hopkins is testing phenylbutyrate, a drug that also helps chaperone mutated CFTR to the cell surface. A pilot trial suggests the drug could partially restore chloride transport in key cells.
-- Duramycin is a failed antibiotic that researchers recently discovered also may help cystic fibrosis, allowing chloride to escape cells by a different route so it does not need the mutated CFTR. First-stage testing of an inhaled version is to begin this fall, Zeitlin said.
Scientists hope gene therapy to correct the cystic fibrosis defect might eventually cure the disease, but progress is slow. That is why doctors are anxiously watching this new gene-assist therapy.
"While we're waiting around for gene therapy ... we have got to do something," Pollard said. "This is something that could actually work."
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