Daijiworld Media Network - New Delhi
New Delhi, Mar 12: A new experimental drug, Nerandomilast, has shown potential in reducing lung inflammation and fibrosis in preclinical models of Idiopathic Inflammatory Myopathy–Associated Interstitial Lung Disease (IIM-ILD), offering hope for improved treatment options for the rare condition.
IIM-ILD is an autoimmune disorder that affects the lungs and is often associated with inflammatory muscle diseases. The condition can lead to progressive lung damage, pulmonary fibrosis and severe breathing difficulties, and currently has limited treatment options.
Researchers investigated whether Nerandomilast, a phosphodiesterase 4B inhibitor that regulates cyclic adenosine monophosphate metabolism in lung tissue, could help control the inflammatory pathways involved in the disease.
To study its effects, investigators developed a preclinical mouse model of IIM-ILD by immunising mice with skeletal muscle homogenate. The animals were then treated with Nerandomilast twice daily at doses of 5 mg/kg and 12.5 mg/kg, while another group received Nintedanib once daily as a positive control.
The study found that treatment with Nerandomilast significantly improved disease indicators in the experimental model. Researchers observed notable reductions in muscle inflammation, lung inflammation and pulmonary fibrosis in treated mice.
Further analysis revealed that the drug also influenced immune activity in lung tissue. It reduced the infiltration and proliferation of B cells in the lungs and lowered the expression of BAFF, a marker associated with immune activation. The treatment also suppressed the differentiation of B cells into plasma cells by reducing the expression of key transcription factors and plasma cell markers.
Blood tests in the study showed a reduction in positivity for Anti-Jo-1 autoantibodies after treatment, suggesting that the drug may help curb the autoimmune processes linked to the disease.
Molecular studies further indicated that Nerandomilast increased intracellular cyclic adenosine monophosphate levels in lung tissue. This was associated with suppression of several immune signalling pathways, including PI3K/AKT signaling pathway, NF-κB signaling pathway and STAT3 signaling pathway in B cells. At the same time, phosphorylation of the transcription factor CREB increased.
Researchers said these findings indicate that Nerandomilast may regulate immune signalling networks involved in B-cell activation and the production of harmful antibodies.
The investigators concluded that the drug could emerge as a promising therapeutic candidate for idiopathic inflammatory myopathy-associated interstitial lung disease, although further clinical research will be required to confirm its safety and effectiveness in humans.