New Class of Kinase Inhibitors Are Potential COPD Anti-inflammatory Therapies
A new class of kinase inhibitors shows promising anti-inflammatory effects in airway cells of patients with chronic obstructive pulmonary disease (COPD), according to a collaborative research study.
The study, “Superior anti-inflammatory effects of narrow-spectrum kinase inhibitors in airway smooth muscle cells from subjects with chronic obstructive pulmonary disease,” was published in the Journal of Allergy and Clinical Immunology.
COPD is characterized by excessive airway inflammation in response to the inhalation of noxious particles. Current therapies for COPD are only able to reduce disease symptoms and progression, so there is an unmet need for an effective treatment for this disease.
Inhaled corticosteroids are commonly used as an anti-inflammatory treatment for COPD. Combined with bronchodilators (which open the airways of the lungs), they were shown to improve lung function, reduce disease progression, and increase quality of life, compared to a single therapy.
However, corticosteroids can have limited therapeutic value in COPD patients, as most patients develop corticosteroid resistance — which means they become less responsive to that treatment.
Inflammatory cytokines are associated with chronic inflammatory disorders and corticosteroid resistance. Cytokines are small secreted proteins important for cell communication, and they are regulated by protein kinases.
Kinases are enzymes that phosphorylate proteins — they add a phosphate group — leading to their activation within cells. Recently, more attention has turned to the therapeutic potential of kinase inhibitors in inflammatory diseases.
Single kinase inhibitors that selectively suppress a type or a family of protein kinases have been previously tested in preclinical studies and moved to clinical trials. However, as kinases have redundant functions, the suppression of one type may be compensated by the activity of other types of protein kinases.
Now, a collaboration between doctors and medical teams in Germany and RespiVert, a subsidiary of Janssen Biotech, investigated the therapeutic potential of two narrow-spectrum protein kinase inhibitors (NSKIs) — RV1088 and RV568 — in COPD.
NSKIs are a new class of kinase inhibitors that suppress specific protein kinase families at the same time.
The study evaluated the effectiveness of RV1088 and RV568 (identified by RespiVert) to suppress inflammatory cytokines in airway cells taken from COPD patients. The results were compared with the effects of a conventional corticosteroid and of three single kinase inhibitors — doramapimod, Sprycel, and R343.
Both NSKIs were found to be more effective in suppressing the production of inflammatory cytokines than the other therapies.
“Our study has demonstrated that NSKIs are promising candidates for the development of urgently required anti-inflammatory COPD therapies,” Jürgen Knobloch, PhD, the study’s first author, said in a press release.
The team believes that these preclinical findings introduce RV1088 and RV568 as promising new therapies for COPD. These compounds are currently being developed in a clinical program to be tested in patients in future clinical trials.