Co-administration of deflazacort and doxycycline: a potential pharmacotherapy for Duchenne muscular dystrophy

Autor(es)

Pereira, Juliano Alves ^[1] ; Marques, Maria Julia ^[1] ; Santo Neto, Humberto ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical and Experimental Pharmacology and Physiology; v. 42, n. 7, p. 788-794, JUL 2015.
• Citações Web of Science: 3

Resumo

The standard therapy used in the treatment of Duchenne muscle dystrophy (DMD) is corticoids, such as deflazacort and prednisone. However, they have limited therapeutic value, and their combination with drugs already in use to treat other human diseases could potentially increase corticoid outcomes in DMD. In the present study, we evaluated whether a combined therapy of the corticoid deflazacort with doxycycline could result in greater improvement in mdx dystrophy than deflazacort alone. Deflazacort alone or deflazacort/doxycycline were administered for 36days (starting on postnatal day 0) in drinking water. Histopathological, biochemical (creatine kinase), functional (forelimb muscle grip strength and fatigue) parameters and inflammatory markers (MMP-9, TNF-, NF-kB) were evaluated in biceps brachii and diaphragm muscles of the mdx mice. The combined therapy was superior in improving the dystrophic phenotype compared to monotherapy. The primary results were observed in attenuating muscle fatigue, decreasing muscle total calcium and inflammatory markers and increasing -dystroglycan, a main component of the dystrophin-protein complex. Furthermore, the combined therapy was effective in preventing the loss of body mass observed with deflazacort alone at this very early stage of therapy. The present study offers preclinical data to support further studies with deflazacort/doxycycline combined therapy in DMD clinical trials. (AU)

• Processo FAPESP: 08/58491-1 - Mecanismos de proteção da distrofia muscular: estudo proteômico e terapia farmacológica
• Beneficiário: Maria Julia Marques
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/04782-6 - Estudos pré-clínicos no camundongo mdx: metabolômica, biomarcadores e terapia com ômega-3
• Beneficiário: Maria Julia Marques
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/51697-6 - Mecanismos de acao do acido eicosapentanoico (epa) na protecao a mionecrose em fibras musculares distroficas
• Beneficiário: Maria Julia Marques
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/15526-9 - Proteínas reguladoras do cálcio e proteção à mionecrose na distrofia muscular de Duchenne
• Beneficiário: Maria Julia Marques
• Linha de fomento: Auxílio à Pesquisa - Regular