Debio-025 is more effective than prednisone in reducing muscular pathology in mdx mice.

Neuromuscular Disorders : NMD
Erin R WissingJeffery D Molkentin

Abstract

Muscular dystrophy results in the progressive wasting and necrosis of skeletal muscle. Glucocorticoids such as prednisone have emerged as a front-line treatment for many forms of this disease. Recently, Debio-025, a cyclophilin inhibitor that desensitizes the mitochondrial permeability pore and subsequent cellular necrosis, was shown to improve pathology in three different mouse models of muscular dystrophy. However it is not known if Debio-025 can work in conjunction with prednisone, or how it compares against prednisone in mitigating disease in dystrophic mouse models. Here we show that Debio-025 reduced the variations in myofiber cross-sectional areas, decreased fibrosis, and decreased infiltration of activated macrophages more efficiently than prednisone. However the use of prednisone and Debio-025 together had no additional effect on these histopathological indexes. Orally administered Debio-025 also reduced creatine kinase blood levels and improved grip strength in mdx mice after 6 weeks of treatment, and the combination of Debio-025 with prednisone increased muscle function slightly better than prednisone alone. Thus, our results suggest that Debio-025 is as, effective as or slightly better than, prednisone in mitigating...Continue Reading

References

Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·B J PetrofH L Sweeney
May 1, 1996·Journal of Neurology·S C JacobsJ H Wokke
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·N MalloukB Allard
May 3, 2000·The Journal of Cell Biology·B B FridayG K Pavlath
Jun 22, 2002·Current Opinion in Genetics & Development·Madeleine Durbeej, Kevin P Campbell
Sep 11, 2002·Neuromuscular Disorders : NMD·Francesco MuntoniDavid Abraham
Aug 5, 2003·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·M L BianchiL Morandi
May 1, 2004·Circulation Research·Karen A LapidosElizabeth M McNally
Oct 1, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Simon J G St-PierreLynn A Megeney
Feb 1, 2005·The American Journal of Pathology·Annamaria De LucaDiana Conte Camerino
May 26, 2006·The American Journal of Pathology·Stephanie A ParsonsJeffery D Molkentin
Jun 23, 2006·Clinical and Experimental Pharmacology & Physiology·Nicholas P WhiteheadDavid G Allen
Mar 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Luciano MerliniPaolo Bernardi

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Citations

May 13, 2011·The Journal of Pharmacology and Experimental Therapeutics·Benjamin A NacevJun O Liu
Aug 30, 2012·The Journal of Pharmacology and Experimental Therapeutics·Marco Brotto, Eduardo L Abreu
Feb 22, 2014·Human Molecular Genetics·Sanjeewa A GoonasekeraJeffery D Molkentin
Apr 14, 2012·Journal of Aging Research·Kunihiro Sakuma, Akihiko Yamaguchi
May 31, 2014·Human Molecular Genetics·Erin R WissingJeffery D Molkentin
Feb 5, 2015·Cell Metabolism·Jennifer Q Kwong, Jeffery D Molkentin
May 8, 2013·Acta Physiologica·K Hollinger, J T Selsby
Nov 22, 2012·Journal of Cellular Physiology·Camilla PellegriniNadir M Maraldi
Jun 20, 2015·Cell Death and Differentiation·A R Burr, J D Molkentin
Feb 12, 2015·Journal of Muscle Research and Cell Motility·Jennifer Manning, Dervla O'Malley
Sep 3, 2013·Current Opinion in Neurology·Urs T Ruegg
Jan 1, 2016·Expert Opinion on Orphan Drugs·Janelle M Spinazzola, Louis M Kunkel
Jan 12, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Anna StoccoPaolo Bernardi
May 27, 2020·Journal of Molecular and Cellular Cardiology·Michela CarraroPaolo Bernardi

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