Research discovers a promising alternative to steroids

Researchers in the USA have discovered a drug that could replace the corticosteroid drugs such as prednisolone currently used to treat Duchenne MD. In studies in mice the drug – called VBP15 – worked better than prednisolone without the harsh side effects. VBP15 may also prove to be a beneficial treatment for other types of muscular dystrophy where inflammation is present in the muscle. Clinical trials of VBP15 are being planned with an expected start date in 2014.

Corticosteroids such as prednisolone are currently the only medication known to help maintain muscle strength in boys with Duchenne muscular dystrophy. On average boys taking this medication are able to delay use of a wheelchair for three years. However, the harsh side effects have a significant impact on quality of life and prevents them being prescribed at the optimum age – before symptoms appear. Many patients also stop taking the medication due to the side effects which can include weight gain, mood changes, stunted growth, fragile bones, cataracts, high blood pressure, diabetes and increased chance of infections.

Corticosteroids work on the body in several different ways – both suppressing inflammation and interacting with the hormonal systems of the body. So to address the problems with corticosteroids, the researchers synthesized a large number of molecules similar to glucocorticoids but with small changes to each one. They then narrowed them down to one, called VBP15, which retained the good properties of corticosteroids without the side effects. This was subsequently extensively tested in a mouse model of Duchenne MD. These mice have a genetic defect that, like boys with Duchenne MD, prevents them from producing an important structural protein called dystrophin in their muscles. As a result, the muscles are fragile and are damaged when the muscles contract. This damage causes inflammation which is also detrimental to the muscles.

VBP15 was shown to have anti-inflammatory effects that were at least as good as prednisolone and as a bonus it was also found to stabilize the structure of muscle cells – a property that prednisolone does not possess. As a result the muscles of the mice treated with VPB15 were stronger than those treated with prednisolone. Side effects of prednisolone were also eliminated – the mice’s growth was not stunted, the immune system was not suppressed and the bones did not thin.

Treating the mice early, before symptoms arose, gave the best results, but it was also found that treating them later also improved the health of the muscles. The authors suggested that if clinical trials prove that VBP15 is beneficial it may be worth implementing a newborn screening program to allow early diagnosis of boys with Duchenne MD so that treatment could be started early.

Corticosteroids are not usually prescribed to people with other types of muscular dystrophy such as Becker MD because it is not known if the benefit would outweigh the detrimental side effects. However, this research suggests that a drug such as VBP15 could be a valuable treatment for these patients.
The authors of this research paper also suggested that it may be advantageous to use VBP15 in combination with treatments currently being developed for Duchenne MD such as exon skipping these to boost their effectiveness.

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