Fenofibrate showed therapeutic effects in Duchenne muscular dystrophy (DMD) models, according to a new study published in the British Journal of Pharmacology. During the study, treatment with fenofibrate improved muscle function and reduced muscle damage in mdx mice, the most common DMD animal model.
The study showed that fenofibrate inhibited the expression of myostatin protein but not myostatin mRNA in primary myoblasts derived from mdx mice. This inhibitory effect on myostatin was also observed in the gastrocnemius and diaphragm muscles of mdx mice along with inhibition of the atrogin-1 and MuRF1 proteins.
Evidence from the study suggests that fenofibrate protects the myoblasts through the degradation of myostatin proteins. Differentiation of myofibers was also found to be enhanced in primary myoblasts via the downregulation of myostatin. Anti-inflammatory effects were also observed in the animals treated with fenofibrate.
“Fenofibrate substantially slows muscle dystrophy by promoting the degradation of myostatin protein, which may indicate a new therapeutic focus for DMD patients,” the authors said.
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Additional study findings include increased myostatin and major histocompatibility complex class I (MHC I) levels in the muscles of DMD patients, as well as mdx mice compared to controls. Serum levels of creatine kinase and lactate dehydrogenase were also found to be elevated in DMD patients compared to controls. The authors hypothesized that this may be due to decreased sarcolemma permeability from a lack of dystrophin.
On several behavioral tests—including a grip strength test, a hanging test, and a rotarod test—mdx mice treated with fenofibrate performed similarly to wild-type mice. Untreated mdx mice performed significantly worse (P <.05) than wild-type and treated mdx mice on all 3 tasks.
Fenofibrate is currently approved by the US Food and Drug Administration for the treatment of hypertriglyceridemia but has also shown pleiotropic benefits for muscle pathologies related to metabolic disorders. Previous studies showed it can reduce inflammation and the accumulation of lipids in myotubes, as well as reduce muscle atrophy through the decrease in expression of myostatin and genes related to atrophy.
Sun Z, Xu D, Zhao L, et al. A new therapeutic effect of fenofibrate in Duchenne muscular dystrophy: the promotion of myostatin degradation. Br J Pharmacol. Published online September 22, 2021. doi:10.1111/bph.15678