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Therapeutic analysis of human immunoglobulin G in a mouse model for Duchenne Muscular Dystrophy

Grant number: 15/19435-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2015
Effective date (End): November 30, 2017
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Mayana Zatz
Grantee:Bruno Ghirotto Nunes
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID


The progressive muscular dystrophies (DMP) are a group of inherited genetic diseases characterized by progressive and irreversible degeneration of skeletal muscle. The Duchenne muscular dystrophy (DMD) is the worst and the most common among the DMPs, affecting 1 in every 3500-5000 boys. Among the conventional treatments for DMD there is the administration of glucocorticoids; however, its long-term use causes numerous side effects. Among the new therapeutic approaches, the treatment of mdx mouse model with IgG resulted in decreased expression of serum creatine kinase (CK) in muscle tissue and less inflammatory markers in the diaphragm material and skeletal muscles. The animals treated with IgG showed improvement in their performance in physical evaluations and less muscle damage. Therefore, IgG appears to be an important contributor to a possible therapy of Duchenne dystrophy. Nevertheless, the main difficulty in using the mdx mouse is that it does not represent the phenotype as seen in patients, since it has light histological changes in the muscle. The aim of this study is to test the immunomodulatory effect of Human Immunoglobulin G (IgG) in experimental mouse models for Duchenne muscular dystrophy, double knockout (DKO) for dystrophin and utrophin genes, whose clinical phenotype is presented as similar as observed in humans who develop the disease.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NUNES, BRUNO GHIROTTO; LOURES, FLAVIO VIEIRA; SIQUEIRA BUENO, HELOISA MARIA; CANGUSSU, ERICA BARONI; GOULART, ERNESTO; COATTI, GIULIANA CASTELLO; CALDINI, ELIA GARCIA; CONDINO-NETO, ANTONIO; ZATZ, MAYANA. Immunoglobulin therapy ameliorates the phenotype and increases lifespan in the severely affected dystrophin-utrophin double knockout mice. European Journal of Human Genetics, v. 25, n. 12, p. 1388-1396, . (15/19435-2, 13/08028-1, 14/04783-2)

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