Steroids
Steroids are hormones that are produced naturally by the body, and can be produced synthetically for use in therapy. Hydrocortisone is the major steroid produced by the cortex of the adrenal gland (hence adrenocortical steroid). The amount of hydrocortisone produced and released into the blood stream varies in a daily rhythm and also in response to stress or danger. It has a broad range of effects in the body at normal physiological doses, which include releasing glucose from tissues (so that it is available for rapid use) and increasing protein breakdown (catabolism) whilst decreasing protein production. However, steroids are largely used therapeutically for their anti-inflammatory and immunosupressive effects at far higher doses than the normal physiological levels. At these doses, the normal functions of the steroids unfortunately become unwanted side effects.
Corticosteroidsteroids in DMD:
The main synthetic steroids used in the treatment of DMD are prednisolone and deflazacort (more recently). Steroids appear to slow progression of muscle destruction and delay the loss of independent walking. The mechanism of action in DMD is unclear, but it is likely that anti-inflammatory effects are very important.
(1) Prednisolone: short-term treatment (6 months) with prednisolone has been shown to increase muscle strength in boys with DMD at both 3 and 6 months, with greater efficacy for daily rather than alternate day dosing. Prednisolone has also been shown to give sustained benefit with longer-term treatment. Over a 15 to 39 month period, prednisolone slowed the decline in muscle strength and functional grade in DMD boys, compared to boys taking placebo. Unfortunately, long term treatment with prednisolone is associated with a number of different side effects. These include weight gain, cushingoid appearance, decrease in predicted height, cataracts, glucose intolerance, acne, increased blood pressure, loss of bone density, emotional lability / irritability, insomnia and behavioural difficulties. However, each individual does not show the same profile of adverse reactions, and some boys show very few side effects at all.
(2) Deflazacort: A recent study comparing deflazacort (another synthetic adrenocortical steroid) and prednisolone showed no difference between the outcome after 12 months in terms of function or muscle strength. Weight gain was greater in the prednisolone group, but other adverse effects were minimal (behavioural changes, increased appetite) in both groups and there were no incidents of abnormally raised blood pressure, acne or insomnia. One boy out of nine in the prednisolone group and two out of nine in the deflazacort group developed cataracts. 2 A longer term study of the efficacy of deflazocort (3.2 years average duration of treatment) compared to no treatment, found that a significantly greater proportion of the steroid treated group were still walking at 10 years of age and there was also a significant beneficial difference in objective measures of lung function. One third of the treated boys developed cataracts, and as a group they showed a smaller gain in height compared to the untreated boys. However, there were no other significant side effects reported.
In summary, corticosteroids have been shown to be effective in increasing muscle strength in boys with DMD. Steroids are by no means a cure, but they do appear to give sustained benefit for at least three years.
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