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Two recent studies, one from Italy and the other from Australia have shown positive effects of anti-inflammatory drugs on dystrophic muscles.
The Australian study by Hodgetts et al (Neuromuscular Disorders 16 (2006) 591-602) used Etanercept, a highly specific anti-inflammatory drug that is widely used clinically to reduce symptoms of inflammatory diseases such as rheumatoid arthritis and Crohn's disease. In this study the muscles of young mdx mice were examined for histologic changes following injection of Entracept. At 21 days of age, the muscle necrosis was markedly reduced in the Entracept treated mice when compared to untreated mdx mice.
A further study was conducted to examine the effect of the Entracept on the muscles of exercised mdx mice, mice allowed to run freely for 48 hours. The muscles from the exercised Entracept treated mice also had a marked reduction in necrosis when compared to the untreated mice that were allowed to exercise. This animal study suggests that Entracept could be tested in a clinical trial to determine its efficacy in boys with DMD. It is already approved for other uses by the FDA and does not have the side effects seen with the prolonged use of corticosteroids.
The Italian study (PNAS 104 (2007) 264-269) examined the use of another anti-inflammatory agent, HCT 1026, in mouse models of Duchenne muscular dystrophy (DMD) and type 2D limb-girdle muscular dystrophy (LGMD2D). In this study the animals were fed HCT 1026 in their regular chow for one year. The muscles from these animals were compared to those from prednisolone treated animals and untreated animals. The LGMD2D mice had reduced serum creatine kinase levels, were able to perform better on a treadmill and moved better voluntarily when compared to the untreated animals. In measurement of muscle strength, the HCT 1026 mice were superior to the untreated. In these measures, the HCT 1026 mice were the same as or better than the prednisolone treated mice without the adverse side effects seen with the steroid treatment. The authors concluded that the results of this work warrant the move to clinical trials of HCT 1026 in patients.
Another benefit found with the HCT 1026 treatment was the enhancement of engrafting the muscles with a type of stem cell that has been shown to correct the genetic defect in the muscle. This is a step toward ameliorating the problem of inefficient grafting of stem cells in the muscles.
