Duchenne Muscular Dystrophy Study Using Golden Retriever Reveals NBD Delivery Improves the Disease Phenotype

A new study entitled “NBD delivery improves the disease phenotype of the golden retriever model of Duchenne muscular dystrophy” published in Skeletal Muscle journal reports the results of a trial with an inhibitor of NF-κB, (NEMO)-binding domain (NBD) peptide, in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a form of muscular dystrophy that is caused by a mutation of the Dystrophin gene, located in the X chromosome. Dystrophin protein is an essential component of muscle tissue. Its loss or deficiency leads to muscle degeneration, mainly in the muscle of legs and pelvis, but it progresses to other muscles, including cardiac muscle. Previous studies associated DMD with constitutive activation of NF-κB (short for nuclear factor kappa-light-chain-enhancer of activated B cells), a key component of the immune response among other cellular processes. In DMD mouse models, inhibition of NF-κB improved diaphragm and cardiac muscle function. Blocking NF-κB signaling was achieved with NF-κB essential modulator (NEMO)-binding domain (NBD) peptide.

In this study, the authors established a golden retriever muscular dystrophy (GRMD) canine model of DMD. GRMD and wild-type control dogs were treated intravenously with NBD over the course of four months. When compared to untreated GRMD and wild-type dogs, NBD treated GRMD dogs exhibited muscle improvements, specifically, recovery of pelvic limb muscle force and decreased tissue injury. These were accompanied with normalized postural changes. However, NBD administration over time triggered immune responses in both treated GRMD and wild-type dogs.

The GRMD trial identified the significant improvements of NBD in a DMD canine model while it identified probably secondary effects and safety concerns that will need to be addressed in potential future human trials.

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