Droga doadora de óxido nítrico diminui a inflamação em um modelo de distrofia de cinturas em camundongos.
Itália – A inflamação desempenha um papel crucial na remodelação e reparação muscular após a lesão aguda e crónica, em particular no distrofias musculares, um grupo heterogêneo de doenças genéticas que levam à degeneração muscular. Defeito da geração de óxido nítrico (NO) é um evento-chave na patogënese das distrofias musculares, portanto, doadores têm sido explorados como novas terapêuticas para esta doença. Os autores investigaram o efeito imuno-modulador de uma dessas drogas, molsidomina, capazes de retardar a progressão da distrofia muscular em camundongos com distrofia tipo cinturas A molsidomina já foi liberada para uso em seres humanos. Os animais tratados apresentaram menor processo inflamatório e reduzida fibrose muscular com o tratamento.
O resumo em inglês pode ser lido abaixo:
(European Journal of Pharmacology, 2013) The Nitric Oxide-donor molsidomine modulates the innate inflammatory response in a mouse model of muscular dystrophy
Paola Zordan, Clara Sciorati, Lara Campana, Lucia Cottone, Emilio Clementi, Patrizia-Rovere Querini, Silvia Brunell
Inflammation plays a crucial role in muscle remodelling and repair after acute and chronic damage, in particular in muscular dystrophies, a heterogeneous group of genetic diseases leading to muscular degeneration. Defect of nitric oxide (NO) generation is a key pathogenic event in muscular dystrophies, thus NO donors have been explored as new therapeutics for this disease. We have investigated the immune-modulating effect of one of such drugs, molsidomine, able to slow the progression of muscular dystrophy in the α-Sarcoglican-null mice a model for the limb girdle muscular dystrophy 2D, sharing several hallmarks of muscle degeneration with other muscular dystrophies. α-Sarcoglican-null mice were treated with molsidomine and drug effects on the inflammatory infiltrates and on muscle repair, were assessed at selected time points. We found that molsidomine treatment modulates effectively the characteristics of the inflammatory infiltrate within dystrophic muscles, enhancing its healing function. Initially molsidomine amplified macrophage recruitment, promoting a more efficient clearance of cell debris and effective tissue regeneration. At a later stage molsidomine decreased significantly the extent of the inflammatory infiltrate, whose persistence exacerbates muscle damage: most the remaining macrophages displayed characteristics of transitional population, associated with reduced fibrosis and increased preservation of the muscle tissue. The dual action of molsidomine, the already known NO donation and the immunomodulatory function we now identified, suggests that it has a unique potential in tissue healing of chronic muscle damage. This, alongside its already approved use in human, make of molsidomine a drug with a significant therapeutic potential in muscular dystrophies.
