For the tens of millions of asthma patients, there is better hope now with American scientists, one of them an Indian-origin, finding out an enzyme known for its role in heart disease, which may prove to be a promising target to treat asthma. According to researchers from the University of Iowa, an enzyme called CaMKII is linked to the harmful effects of oxidation in respiratory tract, which triggers asthmatic symptoms. The finding could lead to development of a drug that could target the CaMKII enzyme.
Asthma affects tens of miillions of people worldwide and 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 in the journal Science Translational Medicine. "The take-home message is that inhibiting CaMKII appears to be an effective anti-oxidant strategy for treating allergic asthma," Anderson said.
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 oxidised CaMKII, no airway muscle constriction and no asthma symptoms.
Similarly, mice without the blocked enzyme showed high 'oxidative stress,' meaning lots of oxidised 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," said Anderson. The researchers also took tissue samples from the airways of patients with asthma. True to their hypothesis, they found more oxidised 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 oxidised CaMKII in the epithelial cells just a day later."We have this very compelling association," Anderson said, adding that more studies in patients are needed to validate the approach. The paper's first author is Philip Sanders, a former postdoctoral student in Grumbach's lab and contributing authors from the UI include Olha Koval, Omar Jaffer, Anand Prasad and others.
