There is an apparent connection between sphingolipid metabolism and Duchenne muscular dystrophy (DMD), according to the results of a recent study published in Science Advances.

The authors used pharmacological inhibition of de novo sphingolipid synthesis in a mouse model of DMD, which alleviated muscle function loss, reduced inflammation, prevented fibrosis, and improved calcium homeostasis of the skeletal muscle, heart, and diaphragm.

Sphingolipids have been linked to several other diseases, including Alzheimer’s disease and cardiovascular disease, and they have been shown to accumulate in the skeletal muscles of obese patients. In this study, the authors found that in myoblasts from patients with DMD, there was an almost ubiquitous upsurge of sphingolipid biosynthetic enzymes, except for ceramide synthase 1.

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“Myoblasts derived from patients with DMD displayed higher fold changes in sphingolipid levels relative to controls than skeletal muscle of mdx mice, which primarily accumulated very-long-chain sphingolipids,” the authors wrote.

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To block sphingolipid synthesis, the authors administered intraperitoneal injections of myriocin (0.4 mg/kg, 3 times per week for 6 months), an inhibitor of serine palmitoyltransferase (SPT), an enzyme encoded by the subunits SPTLC1 and SPTLC2.

Interestingly, this pharmacological inhibition of de novo sphingolipid synthesis reduced muscle function loss, decreased inflammation, improved calcium homeostasis, prevented fibrosis of the skeletal muscle, heart, and diaphragm, and restored the balance between M1 and M2 macrophages. Myriocin was more efficacious than glucocorticoids in DMD model mice.

The authors concluded that an association between sphingolipid synthesis and DMD exists; similarly, reducing sphingolipid synthesis with myriocin improved the health of the model mice in this study. 

“In the present study, we establish the involvement of sphingolipid metabolism pathway in muscular dystrophy. We demonstrate that intermediates of the sphingolipid de novo synthesis pathway accumulate in dystrophic muscle and that sphingolipid levels are elevated in the plasma of mdx mice,” they said.


Laurila PP, Luan P, Wohlwend M, et al. Inhibition of sphingolipid de novo synthesis counteracts muscular dystrophy. Sci Adv. 2022;8(4):eabh4423. doi:10.1126/sciadv.abh4423