Allergic Asthma Clinical Research might have found the answer…
We may be one step closer to understanding the root-cause of allergic Asthma.
The results of a very important laboratory study in mice were published in Science on August 16, 2013.
Cleavage of Fibrinogen by Proteinases Elicits Allergic Responses Through Toll-Like Receptor 4. By Valentine Ongeri Millien, Wen Lu, Joanne Shaw, Xiaoyi Yuan, Garbo Mak, Luz Roberts, Li-Zhen Song, J. Morgan Knight, Chad J. Creighton, Amber Luong, Farrah Kheradmand and David B. Corry
David Corry (the Senior Author) was interviewed by BioWorld Today (August 16, 2013) and we would like to share some of the report along with his comments:
Corry and his team at Baylor College of Medicine in Houston, TX found that TLR4 signaling does not directly activate T cells. Instead, it leads to expression of the interleukin-13 receptor, with the result that T-cell signaling leads to the typical symptoms of asthma. One unexpected discovery was the identity of the ligand that activated TLR4 in their experiments, or at least, its precursor. It was already known that proteases can set off asthmatic symptoms. In their experiments, Corry and his team showed that proteases do so by cleaving or cutting a protein best known as part of the clotting cascade – fibrinogen. After an injury, fibrinogen is cleaved by proteases to make fibrin, which is the protein that initiates the blood clotting process. During an asthma attack, “the same thing is happening in your lings,” Corry said. With one key difference: a part of the precursor molecule then activates TLR4. Corry said he and his team are in the process of working out its exact identity. The findings suggested that once it is clear exactly which part of fibrinogen sets off TLR4 signaling after cleavage, then that molecule could be blocked, perhaps via a monoclonal antibody. Corry said that blocking all TLR4 signaling would be unwise, since doing so “would make people very susceptible to a wide variety of pathogens.” In their experiments, Corry and his team used a fungus as source of the proteases that set off the allergic signaling.
Corry contended that fungal infections are major contributors to asthma. If that idea is true – “and I stress,” he said, “that we have not proven this yet” – the implications are wide-ranging. In the most practical terms, for any asthma treatment to be successful, “you’d better make sure you are treating the underlying fungal infection” in addition to interrupting fi brinogen signaling through TLR4. More generally, the notion that asthma results as a side effect of the immune system doing what it was meant to do – namely, fighting infections – is at odds with the hygiene hypothesis. This explanation for the rapid rise in allergies that has been observed over the past few decades holds that the typical environment of a modern human essentially does not have enough pathogens in it to keep the immune system busy, and so it overreacts to harmless stimuli. (Corry does not support this theory). In Corry’s opinion, it is more likely that the opposite is true: “Our modern, air-conditioned, carpeted environment . . . is the perfect, climate-controlled environment for growing those fungi,” he said. “Every time you walk on a plush carpet you are stirring up those spores . . . and some people just can’t handle the additional amounts of fungus in our environment,” probably due to as-yet undiscovered genetic susceptibility. “At the end of the day, this is a systemic genetic issue.” Corry said there is evidence that eczema and other allergic skin reactions start out as fungal infections, with bacterial coming into play only later. And he believes that gastrointestinal inflammatory diseases may also be found to have a fungal component. To date, that idea is speculation, he said. “But those are the sorts of things we will be looking at.”
Ultimately, the study team concludes, “Clarification of the contribution of true infections to common allergic airway disorders such as allergic rhinitis, asthma, and chronic rhinosinusitis will determine the usefulness of interrupting Fibrinogen Cleavage Products-TLR4 signaling as a therapeutic strategy”.
WCCT Global has conducted over 150 clinical trials of new asthma and allergy medications since 1998. WCCT Global has been privileged to help develop numerous oral and inhaled asthma medications and has been working with several of the “cutting edge” researchers in asthma who are investigating novel, sophisticated pathways of the disease in the hopes to identify a cure for allergic asthma one day soon. Allergic Asthma Clinical Research is specialty of our that we continually expand in. WCCT Global has also participated in the seasonal and perennial allergy development programs for every antihistamine pill, nose and eye drop presently available. WCCT Global has conducted research in asthma and allergy products in children and adults and has research facilities which are specifically configured to accommodate patients of any age.