A new biological mechanism related to an immune response that triggers asthma was discovered by UCSD researchers in collaboration with scientists from Korea University and the University of Aberdeen. This mechanism, if selectively controlled, could be a focus for future treatments that would reduce asthma and other allergic diseases.
In a study published last week in the Proceedings of the National Academy of Sciences, researchers demonstrated that dendritic cells, a type of white blood cell, are a significant player in the overall biochemical pathway leading to asthma as an allergic response.
The concentration of a molecule called cyclic adenosine monophosphate in these cells was found to control the response. When levels of cAMP in DC reach an extreme, a class of immune cells called T-helper 2 cells is signaled in such a way that they induce allergic asthma.
The relationship between DC and T-helper cells is of particular interest to researchers. While asthma is one type of disease that is specifically linked to T-h2, there are a number of other allergic diseases induced by other T-helper cells, which are signaled to act as a result of cAMP levels in DC. Understanding this relationship in depth would then open the door to developing treatments that could maintain an appropriate level of cAMP in DC and prevent allergic diseases, either through drugs or therapy.
Dr. Paul Insel, co-author and professor of pharmacology and medicine at UCSD, told the UCSD Guardian that developing a drug to control cAMP levels in DC would be the next step in asthma research.
“There aren’t any drugs [currently] that can control the levels of cyclic AMP, and those drugs would be a logical approach for treating the dendritic cells and raising the cyclic AMP levels so that we wouldn’t see [the development of asthma],” Insel said. “And we’re testing that in experiments now. The kinds of drugs that [control cAMP levels] are widely used, but we don’t know which ones to use in the dendritic cells.”
Another significant feature of this study was that the genetics of the mice used, which led to a missing protein that was speculated to regulate the cAMP levels, did in fact result in the mice contracting asthma spontaneously, much like humans do. Dr. Eyal Raz, principal investigator and professor of medicine, told the Guardian that this was a major advantage of this study.
“One problem that the scientific community has [with asthma research] is that you have to work very hard for the mice to develop the asthma,” said Raz. “And then people say [the study] you have [done] here has nothing to do with human disease. Here [in our study], [the mice] developed spontaneous asthma.”
Insel added that these protein-lacking mice resemble the clinical conditions of human patients more closely than any others used in any other study before.
“There’s a long list of studies that has been done in mice that have not panned out when the studies were transferred to patients,” Insel said. “And we believe that this model appears to be much more closely matched to the human disease, so these mice might actually turn out to be a lovely system for testing new asthma therapies and other conditions.”
For Insel’s group, the next immediate step will be to look for receptors that can activate the protein involved in producing cAMP for DC in order to direct drug research toward possible receptors to target. They expect to obtain the results of their next project quickly.
“We’re hoping to advance [our research] within the next year,” said Insel.“We’re waiting to hear about getting some federal funding, and if we do, that will really accelerate this project. So we’ve got our fingers crossed.”