Inibição dos receptores dos mineralocorticóides: um novo alvo para terapia da distrofia muscular de Duchenne
USA – nesta pesquisa os autores estudaram a inibição dos receptores dos mineralocorticóides que foram associados com espironolactona e lisinopril resultando em um dramático aumento da força muscular e respiratória com menor alterações patológicas dos músculos.
O resumo em inglês pode ser lido abaixo:
(Experimental Biology, 2015) Elucidating the Role of Mineralocorticoid Receptors in Skeletal Muscle as a Potential Therapeutic Target for Duchenne Muscular Dystrophy
Jessica Chadwick, James Hauck, Jeovanna Low, Jill Rafael-Fortne – USA
Our lab identified a potential new treatment for Duchenne Muscular Dystrophy using the mineralocorticoid receptor (MR) antagonist spironolactone and ACE inhibitor lisinopril. Drug studies using dystrophic Het (utrn+/-;mdx) mice showed a dramatic improvement in both respiratory and limb muscle force and a reduction of ongoing muscle damage, in addition to preventing cardiomyopathy. We show MR is present in both skeletal muscle tissue and myogenic cultures , supporting a direct affect by MR antagonists on skeletal muscle. Global analysis of gene expression between treated and untreated dystrophic mice identified potential molecular targets to unravel the drugs’ mode of action. Preliminary microarray data comparing quadriceps muscle from lisinopril and spironolactone treated het mice to untreated controls revealed changes in the expression of several gene targets with known roles in striated muscle, which have been confirmed using immunofluorescence and western blot analysis. Myogenic cultures treated with MR agonists and antagonists are being used to test whether these potential downstream targets are affected in a cell autologous manner in skeletal muscle and represent bona fide MR gene targets. NIH 1 R01 NS082868; T32 NS077984
