making muscle wasting history

At the annual meeting of Action Duchenne in London in November 2007, Prof. Adnan Manzur of the Hammersmith Hospital in London gave an overview of the actual state of steroids treatment, presently the only drug treatment proven to be able to preserve or maintain the muscles of Duchenne boys for a limited time.
This type of treatment is now considered the “gold standard” to which other treatments in development are compared. Up to now, 47 clinical studies have been performed in many countries, but only six of them were scientifically important double-blind studies with fully published results. In most studies, daily application of the drugs were investigated, but some other regimes, like 10 days with medication followed by10 days without (“10 days on, 10 days off”), or medication for only 10 consecutive days each month were also tried. Some of the more important results are:
The first of the double-blind studies was performed in 1991 by Fenichel et al. in the US with 99 boys who received 0.75 mg/kg/day prednisone for two years. The results showed for the first time in a scientifically reliable way that this treatment improved and stabilized the muscle strength of Duchenne boys for about three years. But 73% of the boys had side effects, mostly excessive weight gain.
In a double-blind study in Germany by Reitter et al. in 2000, the two steroid drugs prednisone and deflazacort were tested in 100 boys. Weight gain was significantly higher in the prednisone-treated boys than in the deflazacort-treated ones. But deflazacort led to many more rather benign cataracts (turbidity in the eye lenses) than prednisone.
This study has not been fully published. In 2006 Biggar et al. in Canada published the results of a long-term but open study with 74 boys who were 10 to 18 years old, 40 of whom were treated daily with deflazacort at 0.9 mg/kg/day for an average time of 5.5 years. The 34 non-treated boys lost their ambulation at 9.8 years. Of the treated boys, 81% could still walk at 12 years, 76% at 15 years, and 30% at 18 years. Breathing and heart function remained significantly better and scoliosis (deformation of the spine) developed less often in the treated boys. King et al. in the US reviewed 2007 the clinical history of 143 boys, 75 of whom were treated daily with mainly deflazacort for an average of 8 years, and 68 were not treated. The treated boys could walk 3.3 years longer and had a significantly decreased risk of scoliosis than the untreated
ones. But they had an increased risk of vertebral and lower limb fractures due to osteoporosis compared with the untreated boys. Dr. Manzur concluded his review with the following take-home message: The long-term use of the steroids prednisone (and the very similar prednisolone) and deflazacort improve muscle strength and function and prolong walking for several years, improve breathing and heart function, lower the risk of scoliosis and enhance the quality of life. The positive effects appear to be more pronounced if the treatment is started early, at about four years, and if the drugs are given daily. The side effects, especially of prednisone, are increased appetite which may lead to excessive weight gain and cushingoid face (moonfaced) unless a diet rich in proteins and low in fat and carbohydrates is strictly followed from the beginning of the
treatment. Both drugs lead to reduced growth and increased
risk of bone fractures, and to some behavioral changes. Deflazacort gives rise to some rather benign cataracts which need not to be treated.

As further research is needed, the North Star Clinical Network, a collaboration of 15 centers in the UK with the British parents’ organizations Muscular Dystrophy Campaign and ActionDuchenne, is planning to optimize and standardize the steroid therapy of ambulant Duchenne boys by creating a national clinical database, and to offer daily and intermittent steroid treatment to all Duchenne boys from age four years onwards, or even earlier, with scientific and clinical checks and investigations before, during and after the treatment. TREAT-NMD, the European neuromuscular network, has published 8 pages of preliminary recommendations for standards of care in Duchenne muscular dystrophy, among them about the use of corticosteroids.