A collaborative study, published in the Journal of Allergy and Clinical Immunology, demonstrated the potential of a new class of drugs for the treatment of chronic obstructive pulmonary disease (COPD). According to the authors of the study, the new drugs may potentially constitute a breakthrough in the treatment of COPD.
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. Currently, available inhaled corticosteroids help alleviate only the symptoms of COPD and provide some benefit in the prevention of acute exacerbations.
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 the researchers, Narrow Spectrum Kinase Inhibitors (NSKI) that inhibit protein kinases constitute a promising therapeutic approach. Two NSKIs – namely RV1088 and RV568, which were identified and provided by RespiVert for the studies – were tested by the team in cell cultures.
The researchers compared their efficacy with a conventional corticosteroid and various Single Protein Kinase Inhibitors, which are likewise considered potential drug candidates. The NSKIs were more effective in decelerating the production of inflammatory agents than any of the reference substances.
A number of small molecule inhibitors of specific single kinases have previously been successfully tested in preclinical trials and advanced to clinical studies. These substances 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," said Jürgen Knobloch, head of the 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 team tested new drug candidates that target 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.