An enzyme known for its role in heart disease may well be a promising target to treat asthma. Researchers from the University of Iowa have found that the enzyme, called CaMKII, is linked to the harmful effects of oxidation in the respiratory tract, triggering asthmatic symptoms. The finding could lead to the development of a drug that would target the CaMKII enzyme, the researchers say.
Asthma affects billions of people worldwide. In the United States, 8.5 percent of the population has asthma, which causes 3,000 deaths and more than $56 billion annually in medical and lost work costs, according to the federal Centers for Disease Control and Prevention. Despite its toll on health and productivity, treatment options remain confined to steroids, which have harmful, even life-threatening, side effects for those with severe cases.
Current treatments don’t work well, noted Mark Anderson, professor and chair in internal medicine at the UI and a co-corresponding author on the paper, published July 24 in the journal Science Translational Medicine.
“It’s a kind of an epidemic without a clear, therapeutic option," Anderson says. "The take-home message is that inhibiting CaMKII appears to be an effective anti-oxidant strategy for treating allergic asthma."
Anderson and co-corresponding author Isabella Grumbach knew from previous work that the CaMKII enzyme played a role in the oxidation of heart muscle cells, which can lead to heart disease and heart attacks. The scientists surmised the same enzyme may affect oxidation in the respiratory system as well.
The team first tested the enzyme in airway muscle cells, but to little effect. They then tried to block the enzyme in the airway lining (epithelial) cells. They noticed that mice with the blocked enzyme had less oxidized CaMKII, no airway muscle constriction and no asthma symptoms. Similarly, mice without the blocked enzyme showed high “oxidative stress,” meaning lots of oxidized enzymes in the epithelial cells, a constricted airway and asthma symptoms.
“[The study] suggests that these airway lining cells are really important for asthma, and they’re important because of the oxidative properties of CaMKII,” says Anderson, whose primary appointment is in the Carver College of Medicine. “This is completely new and could meet a hunger for new asthma treatments. Here may be a new pathway to treat asthma.”
"Ten years ago, not much was known about what CaMKII does outside of nerve cells and muscle cells in the heart," says Grumbach, associate professor in internal medicine at the UI. "My lab has worked on investigating its function mainly in blood vessels with the long-term goal to use blockers of CaMKII to treat common diseases. We are constantly finding that CaMKII is interesting and important."
The researchers also took tissue samples from the airways of patients with asthma. True to their hypothesis, they found more oxidized enzymes in those patients than in healthy individuals. Taking a step further, the team found that mild asthma patients who inhaled an allergen had a spike in oxidized CaMKII in the epithelial cells just a day later.
“We have this very compelling association,” Anderson says, adding that more studies in patients are needed to validate the approach.
The researchers also plan to investigate inhaled drugs that could block the oxidation of theCaMKII enzyme, for treating heart disease and asthma. Anderson has a patent and is involved in a company, Allosteros Therapeutics, which is seeking to develop such a drug.
The paper’s first author is Philip Sanders, a former postdoctoral student in Grumbach's lab, helped design the study and analyzed much of the data. Contributing authors from the UI include Olha Koval, Omar Jaffer, Anand Prasad, Thomas Businga, Jason Scott, Elizabeth Luczak, David Dickey, Francis Miller, Jr., Megan Dibbern, Joseph Zabner, Joel Kline, Chantal Allamargot, Alicia Olivier, David Meyerholz, Brett Wagner, Garry Buettner and Marshall Pope. Other contributing authors are Patrick Hayden from MatTek Corporation; Alfred Robison from the Mount Sinai School of Medicine in New York; Danny Winder, Timothy Blackwell and Ryszard Dworski from Vanderbilt University; Hans Michael Haitchi, David Sammut and Peter Howarth from the University of Southampton, United Kingdom; and Peter Mohler from Ohio State University.
The National Institutes of Health (grant numbers: K23 HL080030 02 and M01 RR-00095), the American Asthma Foundation and the Sandler Program for Asthma Research funded the work.Contacts
Richard Lewis | EurekAlert!
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering