According to a collaborative study led by assistant professor Dr. Jürgen Knobloch from the Bergmannsheil University Hospital in Bochum, the new substances may potentially constitute a breakthrough in the treatment of Chronic Obstructive Pulmonary Disease (COPD). The study was published in the Journal of Allergy and Clinical Immunology.
COPD patients suffer from chronic inflammation of the respiratory tract. Certain enzymes, so-called protein kinases, regulate the inflammation process. They are indirectly over-activated due to smoking, due to pro-inflammatory factors characteristic of COPD, and due to respiratory infections. This results in the production of even more pro-inflammatory factors, which, in turns, promotes disease progression.
According to expert estimates, COPD currently affects 11.7 percent of the global population. In most cases, the disease starts as chronic bronchitis, and it is mainly caused by smoking tobacco. Current therapies can retard the progression of COPD and provide symptom relief, but they cannot stop it.
Currently available inhaled corticosteroids help alleviate the symptoms of other chronic inflammatory pulmonary diseases and provide some benefit in the prevention of acute exacerbations, but they are currently only recommended for use in combination with bronchodilators and in patients that experience frequent exacerbations.
According to the researchers, Narrow Spectrum Kinase Inhibitors (NSKI) that inhibit protein kinases constitute a promising therapy approach. Two NSKIs – namely RV1088 und RV568, were tested by the team in cell cultures; the researchers compared their efficacy with a conventional corticosteroid and various Single Protein Kinase Inhibitors. The NSKIs were more effective in decelerating the production of inflammatory agents than any of the reference substances.
Previous studies have reported that small molecule inhibitors of specific single kinases selectively inhibit individual protein kinases or a family of protein kinases. "However, it is emerging that the effect would not be sufficient in clinical applications," explained Jürgen Knobloch, head of laboratory at the Pneumology Clinic at Bergmannsheil. "In case of such a specific inhibition, activation of other protein kinases may act to induce similar inflammation."
Therefore, the research team led by assistant professor Dr Jürgen Knobloch from the Bergmannsheil University Hospital in Bochum, tested new drug candidates that target not only one protein kinase or a family of protein kinases, but a specific spectrum of several protein kinase families. In the research lab at the Bergmannsheil Pneumology Clinic, researchers then tested the substances in primary cultures of airway smooth muscle cells taken from COPD patients.
"Our study has demonstrated that NSKIs are promising candidates for the development of urgently required anti-inflammatory COPD therapies," said Jürgen Knobloch. Consequently, the researchers believe that the findings gained in the preclinical model offer an immense potential for a transfer to applications in patient care.