Deflazacort in Duchenne
muscular dystrophy: a comparison of two different protocols
W. D. Biggar L.
Politano, V. A. Harris, L. Passamano, J. Vajsar, B. Alman, A. Palladino, L. I.
Comi and G. Nigro - Canada and Italy
Abstract :
We compare
the long-term benefits and side effects of deflazacort using two treatment
protocols from Naples (N) and Toronto (T). Boys with Duchenne muscular
dystrophy between the ages of 8 and 15 years and who had four or more years of
deflazacort treatment were reviewed. Diagnostic criteria included males with
proximal muscle weakness evident before 5 years, increased serum creatine kinase
and genetic testing and/or a muscle biopsy consistent with Duchenne muscular
dystrophy. Thirty-seven boys were treated with protocol-N using deflazacort at
a dose of 0.6 mg/kg per day for the first 20 days of the month and no
deflazacort for the remainder of the month. Boys with osteoporosis received
daily vitamin D and calcium. Deflazacort treatment started between 4 and 8
years of age. Thirty-two were treated with protocol-T using deflazacort at a
dose of 0.9 mg/kg per day, plus daily vitamin D and calcium. Treatment started
between 6 and 8 years of age. All boys were monitored every 4–6 months. The
results were compared with age-matched controls in the two groups (19 for
protocol-N and 30 for protocol-T). For the boys treated with protocol-N, 97% were
ambulatory at 9 years (control, 22%), 35% at 12 years (control, 0%), 25% at 15
years (control, 0%). For the 32 boys treated with protocol-T, 100% were
ambulatory at 9 years (control, 48%), 83% at 12 years (control, 0%) and 77% at
15 years (control, 0%). No aids or leg braces were used for ambulation. In boys
13 years and older, a scoliosis of >20° developed in 30% of the boys on
protocol-N, 16% on protocol-T and 90% of controls. For protocol-N, no cataracts
were observed while in protocol-T, 30% of boys had asymptomatic cataracts that
required no treatment. Fractures occurred in 19% (control 16%) of boys on
protocol-N and 16% (control, 20%) of boys on protocol-T. This report
illustrates: (a) the importance of collaborative studies in developing
treatment protocols in Duchenne muscular dystrophy and (b) the long-term
beneficial effects of deflazacort treatment in both protocols. However, the
protocol-T seems to be more effective and frequently is associated with
asymptomatic cataracts.
Neuromuscular
Disorders, 2004
Michelle
Wehling-Henricks, James J. Lee and James G. Tidball - USA
The mechanism of prednisolone's
efficacy in the dystrophic pathology is unclear. Prednisolone's
anti-inflammatory functions may be particularly important considering the
significance of inflammatory cells in dystrophinopathy. In other pathologies,
prednisolone's anti-inflammatory effects can be mediated by reducing cellular
adhesion molecule (CAM) expression. The goal of this study was to examine the
effects of prednisolone on inflammation and CAM expression in dystrophic
muscle. Dystrophin-deficient, mdx mice were treated with 0.75 mg/kg
prednisolone from 2 to 4 weeks of age. Prednisolone reduced macrophages
(−59%, −57%), CD4+ T-cells (−50%, −60%), CD8+
T-cells (−58%, −48%), and eosinophils (−36%, −25%) in
quadriceps and soleus muscles, respectively. Prednisolone-treated mice also
exhibited decreased vascular P-selectin (−82%) and ICAM-1 (−52%)
expression and fewer L-selectin (−79%) and ICAM-1 (−57%) expressing
mononuclear cells in quadriceps. Prednisolone reduced sarcolemmal damage and
degeneration as well. Our data show that prednisolone is an effective
anti-inflammatory in dystrophic muscle and may function by modulating CAM
expression.