NBD delivery improves the disease phenotype of the golden retriever model of Duchenne muscular dystrophy

Skeletal Muscle
J N KornegayDenis C Guttridge

Abstract

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene and afflicts skeletal and cardiac muscles. Previous studies showed that DMD is associated with constitutive activation of NF-κB, and in dystrophin-deficient mdx and utrophin/dystrophin (utrn (-/-) ;mdx) double knock out (dko) mouse models, inhibition of NF-κB with the Nemo Binding Domain (NBD) peptide led to significant improvements in both diaphragm and cardiac muscle function. A trial in golden retriever muscular dystrophy (GRMD) canine model of DMD was initiated with four primary outcomes: skeletal muscle function, MRI of pelvic limb muscles, histopathologic features of skeletal muscles, and safety. GRMD and wild type dogs at 2 months of age were treated for 4 months with NBD by intravenous infusions. Results were compared with those collected from untreated GRMD and wild type dogs through a separate, natural history study. Results showed that intravenous delivery of NBD in GRMD dogs led to a recovery of pelvic limb muscle force and improvement of histopathologic lesions. In addition, NBD-treated GRMD dogs had normalized postural changes and a trend towards lower tissue injury on magnetic resonance imaging. Despite this phenotypic improvement, NB...Continue Reading

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Citations

Jul 25, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maliha Zahid, Paul D Robbins
Nov 8, 2016·Neuromuscular Disorders : NMD·Austin R AcostaJoe N Kornegay
May 21, 2017·Skeletal Muscle·Joe N Kornegay
Mar 8, 2018·Muscle & Nerve·William B StoughtonJoe N Kornegay
Aug 28, 2019·Journal of Neuromuscular Diseases·Inès BarthélémyLaurent Tiret
Jan 1, 2016·Expert Opinion on Orphan Drugs·Janelle M Spinazzola, Louis M Kunkel
Mar 29, 2020·Frontiers in Veterinary Science·Brett D StoryHeather L Gray-Edwards
Dec 18, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ling LengHaiFang Yin
Sep 4, 2018·Journal of the American Chemical Society·Curran A RhodesDehua Pei

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Methods Mentioned

BETA
ubiquitination
PCR
force measurements
biopsy
ELISA

Software Mentioned

Microsuite Five
LabView
WinNonlin Professional

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