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STOP-JIA

Of Mice and Men…and Maybe Muscle

By: Kenneth Schikler, MD | July 1, 2016 | What Caught Our Eye

Editor’s Note: We invite readers to engage in the conversation about this topic in the comments section below.

As I am sure occasionally happens to us periodically, a young toddler was referred to me by gastroenterology after being evaluated for hepatopathy regarding elevated “liver enzymes.”  This young boy ended up having muscle disease, and genetic testing confirmed Duchenne Dystrophinopathy. While he has been sent on to our MDA clinic for his future care, I was interested in looking into what was new in Muscular Dystrophy.

In the Proceedings of the National Academy of Sciences (vol 112, no 41, pp 12864-69), Whitehead et al report on “A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy”.  

In both Duchenne dystrophy and dystrophin-deficient mice, muscle degeneration involves chronic inflammation, oxidative stress, and fibrosis. Despite concern about statin-induced muscle disease in humans (<1% compared to placebo), they point out that statins have been associated with improved skeletal muscle health in in ischemic limb disease and diminished oxidative stress and inflammatory cell infiltrate. They treated DMD mice with simvastatin concentrations that would equate with moderate human daily dosing. There was both short-  term and long-term improvement in muscle pathology and physiologic function with reduced inflammation, oxidative stress and fibrosis. Muscle regeneration was not impeded.

The authors conclude that their “data are consistent with the idea that statins are highly beneficial to skeletal muscles afflicted with an underlying disease that involves ischemia, oxidative stress, and inflammation.”  They also point out that atrogin-1 is implicated in statin myopathy. At least in the DMD mice, the atrogin-1 levels in statin-treated mice were lower than wild-type mice and were not significantly different from the levels in DMD controls. They suggest that simvastatin may have the opposite effect on dystrophic muscle compared to normal muscle.

Preusse et al, in “Differential roles of hypoxic and innate immunity in juvenile and adult dermatomyositis” (Acta Neuropathologica Communications 2016, 4:45), demonstrates that juvenile dermatomyositis is tightly linked to hypoxia-related pathology while adult dermatomyositis is interferon-related and that these dichotomous pathways both result in perifascicular skeletal myofibril atrophy.

What might the role of statins be in the management of JDM?  Hmmm?