Blocks inflammatory activity of two immune system molecules, researchers report
THURSDAY, Oct. 18 (HealthDay News) -- A new twist on an old theory of drug treatment for asthma has shown promise in a small, early trial, a California company reports.
The idea is to block the activity of cytokines, immune system molecules believed to play a major role in asthma by causing allergic inflammation.
A number of cytokines have been implicated in asthma, among them interleukin-4 and interleukin-13. A number of drugs aimed at blocking one or the other have met with little success.
The new approach is a single drug, called pitrakinra, which blocks the receptors for both interleukins simultaneously, said Malinda Longphre, director of the clinical department of Aerovance Inc. in Berkeley.
"It has been shown that IL-4 shares receptors with IL-13," Longphre added. "They produce the same response. Our drug blocks the shared receptors, and it appears from the two clinical trials we report that we are able to intervene and inhibit the allergic response throughout."
Results of the two trials are reported in the Oct. 19 issue of The Lancet. In one trial, 12 people with asthma were given daily injections of pitrakinra and then inhaled allergens. One major measure of lung function, forced expiratory volume, was reduced by only 17.1 percent in those taking the drug, compared to a decrease in lung function of 23.1 percent in a group taking a placebo.
In the second study, 16 people with asthma inhaled pitrakinra. The decrease in lung function when exposed to allergens averaged a mere 4.4 percent, compared to a 15.9 percent decrease in lung function for a comparable group that was given placebo.
"The drug itself is human IL-4, with a couple of amino acid substitutions that allow it to bind to the receptors," Longphre explained. The company hopes to market the drug as an inhalant, but that prospect is years away and will require a long series of successful trials, she added.
"We see it as a treatment for problem patients, those not able to control the condition by steroid therapy," Longphre said. "Most doctors have at least one such patient in their practice."
The findings drew a mixed response from asthma experts.
Dr. Harold Nelson, a professor of medicine at the National Jewish Medical and Research Center in Denver, was downbeat, primarily because of his experience with an IL-4 blocker several years ago.
"A first study was fairly encouraging," Nelson said. "A second study was positive. A third study was an utter failure, and we dropped the drug."
And Nelson was not impressed by the nature of the Lancet studies. "These were allergen-challenge studies," he said. "An allergen-challenge study is not asthma. A positive response in an allergen-challenge study is not a positive response in asthma."
However, Dr. Marc E. Rothenberg, director of the division of allergy and immunology at Cincinnati Children's Hospital Medical Center, had a markedly different reaction.
"The idea that a drug can block this pathway and block the asthmatic reaction is very exciting," Rothenberg said.
While the two trials were small, "they were not insignificant," he added. "Such a dramatic effect with a small sample size indicates that the effect will not be trivial."
The new drug is a result of two decades of research, and "key targets have been identified through this molecular research," Rothenberg said.
Drug companies now are testing a number of drugs aimed at blocking cytokine activity in asthma, he added.
For more on asthma and its treatment, consult the National Library of Medicine.
SOURCES: Malinda Longphre, Ph.D., director, clinical department, Aerovance Inc., Berkeley, Calif.; Harold Nelson, M.D., professor, medicine, National Jewish Medical and Research Center, Denver; Marc E. Rothenberg, M.D., director, division of allergy and immunology, Cincinnati Children's Hospital Medical Center; Oct. 19, 2007, The Lancet
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