Saturday, April 07, 2001
Test of CF treatment planned
Early lab findings promising
By Tim Bonfield
The Cincinnati Enquirer
Researchers at the University of Cincinnati and Children's Hospital Medical Center plan to launch a clinical trial this summer to test what could be a breakthrough treatment for cystic fibrosis.
Half the people born with cystic fibrosis die before age 32. But if human testing of an experimental treatment patented by UC lives up to initial hopes, many more cystic fibrosis patients could live a normal life span.
The researchers say much more work needs to be done.
We've seen a nice effect in cells in the lab. But whether we will see an effect on the whole body remains to be seen. That's why we are doing the studies, said Dr. Robert Wilmott, director of pulmonary medicine at Children's Hospital and a leading expert on cystic fibrosis.
The excitement stems from two promising findings presented this week at scientific meetings in Seattle and Orlando.
Dr. John Cuppoletti, a physiologist with UC's department of molecular and cellular physiology, presented lab results on two compounds at the Experimental Biology 2001 meeting in Orlando. One of the compounds is omeprazole, the active ingredient in the heartburn medication Prilosec.
The studies report that both compounds can trigger an alternative way for the body to process salt, a crucial issue for cystic fibrosis patients. The genetic inability of CF patients to properly process salt leads to lung inflammation, excessive mucus build-up and dangerous infections that are the most common cause of death for CF patients.
The hope is that we can activate these other ion channels and repair the defect that causes cystic fibrosis, Dr. Cuppoletti said.
Dr. Wilmott presented preliminary human test results involving the Prilosec compound Monday in Seattle at a research meeting of the Cystic Fibrosis Foundation.
The yearlong study involved 10 volunteers who did not have cystic fibrosis. Their nostrils were irrigated with a liquid version of the Prilosec drug to see if it had any effect on salt levels in their nasal tissue. It did.
We saw some interesting trends, but the results are not statistically significant, Dr. Wilmott said.
The results were positive enough to begin repeating the tests in another 10 normal volunteers. However, reporting success in the lab and an effect in normal people is not the same as reporting a therapeutic effect in CF patients, Dr. Wilmott said.
The next two steps will be key: launching a small study in Cincinnati to see if an effect can be measured in CF patients. If that succeeds, then a multisite clinical trial involving hundreds of CF patients would follow, Dr. Wilmott said.
The national Cystic Fibrosis Foundation is closely following the research efforts in Cincinnati, said Chris Penland, the foundation's research director.
We think the work is very important. If these compounds can increase chlorine secretions and aid in clearing the airways of CF patients, it would be an important advance, Dr. Penland said.
Children's Hospital has a long history of research involving cystic fibrosis, including curing mice of the disease through genetic modifications and testing would-be genetic therapies in humans. For the past three years, Children's Hospital has been one of eight centers nationwide in the Cystic Fibrosis Therapeutic Development Network.
Dr. Wilmott cautioned that cystic fibrosis patients and their families should not assume too much about this new research project.
Dr. Cuppoletti has come up with an excellent idea. It is worth pursuing. But I still think this is in a very early phase, Dr. Wilmott said. We start a lot of things that don't pan out.
A few years ago, after the discovery of the genetic defects causing cystic fibrosis, hope swelled that CF could be conquered with genetic therapy.
However human testing of those treatments, including a major study led by Children's Hospital, proved disappointing. Studies in Cincinnati had to be stopped because the modified cold virus used to carry treatment into the lungs caused too much inflammation.
The Prilosec option Dr. Cuppoletti discovered appears promising because it attacks the most dangerous aspect of cystic fibrosis without relying heavily on genetic therapy.
It also involves a drug that the U.S. Food and Drug Administration has already approved for another use. Should the compound work as a CF therapy, the FDA approval status would cut several years off the time it would take to bring the product to market.
Doctors say much study is needed to see if the Prilosec drug provides a big enough and long-lasting effect to help control cystic fibrosis. Other questions include whether the dose level needed to produce an effect can be tolerated without harmful side effects and how best to administer the drug as a pill, an inhaled mist or another form.
Research has not progressed as far on the second CF-related compound Dr. Cuppoletti patented. That compound has not been used in humans before, which means turning it into a medicine would require years of lab and animal testing before human testing could begin.
That work is on hold to see if the potentially quicker-to-market compound can be successful, Dr. Cuppoletti said.
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