Steroids in muscular dystrophy: Where do we stand?

1. IntroductionThe promise of gene therapy for Duchenne musculardystrophy (DMD) is awaiting future developments in thefield of molecular biology. Moreover, gene replacement orrestitution of dystrophin by means of this technique may notrepresent a cure for the disease. Gene therapy in the treat-ment of muscular dystrophy has met a number of obstacles,including immune reaction to viral vectors, difficulty inpenetrating through the basal lamina and limited spread ofaction to a relatively small number of muscle fibres.Meanwhile, the utilisation of drugs capable of producinga benefit by slowing down the course of the disease seems toafford an alternative path that clinical research should fol-low over the next few years. So far, the only drugs shown toproduce a slowing in the downhill course of the disease havebeen the steroids.Since the first observations by Drachman [1], whenimprovement was originally documented, several reportshave provided positive data on the use of glucocorticoidsin DMD and have already been reviewed up to 1991 in aneditorial paper in this journal [2]. Later reports are includedand summarised in Tables 1, 2 and 3, but a critique of eachstudy is beyond the scope of this current clinical practicereview.More recently, during the 47th International ENMCWorkshop experiences on the use of diverse steroid regimeswere presented by authors from seven countries [16]. Themore relevant conclusions were (a) that there was evidenceof potential value of steroids in DMD treatment, (b) thatfurther multicentric studies following agreed protocolswere essential and (c) that a wide diversity of specific ques-tions had to be answered. Some aspects related to currentknowledge, experience and opinions concerning the use ofsuch therapeutic agents in Duchenne dystrophy are the sub-ject of this clinical-practice review.The mechanisms through which steroids produce clinicalbenefit have not yet been definitively established but thoserelated to protein synthesis and turnover in the muscle fibre,or even those involved in immunological regulation deserveconsideration.Although we have accumulated interesting experiencewith the use of corticosteroids in the last few years, severalquestions regarding the common practice of this treatmentremain unanswered. For some authors, the risks involved inthe long-term use of steroids still preclude their administra-tion, for others, the option is clear but some issues are still amatter of discussion, such as the best patient age to start thetreatment, when withdrawal is appropriate and whether it isworth using the medication for wheel-chair-bound patients.2. Mechanisms involved in steroid action in musculardystrophyOn the basis of the cumulative data summarised in Table1, 2 and 3, there seems to be little doubt about the usefulnessof steroids in DMD but the mechanisms of action involvedin clinical benefit are still a matter of speculation. Fromwhat has been observed in clinical trials, steroids may in-crease muscle mass, since there is an increase in creatinineexcretion [5] in prednisone-treated patients.Further studies on prednisone-treated DMD/Becker mus-cular dystrophy (BMD) patients have suggested that bene-ficial drug effect on strength appears to be related to aninhibition of muscle proteolysis rather than stimulation ofprotein synthesis. In treated patients, the 3-methylhisti-dine–creatinine excretion ratio decreased by 26% [17].