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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Pereira, Juliano Alves [1] ; Marques, Maria Julia [1] ; Santo Neto, Humberto [1]
Total Authors: 3
Affiliation:
[1] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Clinical and Experimental Pharmacology and Physiology; v. 42, n. 7, p. 788-794, JUL 2015.
Web of Science Citations: 3
Abstract

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)

FAPESP's process: 14/04782-6 - Pre-clinical studies in the mdx mouse: metabolomics, biomarkers and omega-3 therapy
Grantee:Maria Julia Marques
Support Opportunities: Regular Research Grants