Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial

Shieh, Perry B.; McIntosh, Joseph; Jin, Fengbin; Souza, Marcio Ferreira de; Elfring, Gary L.; Narayanan, S.; Trifillis, Panayiota; Peltz, Stuart W.; McDonald, Craig M.; Darras, Basil T.

doi:10.1002/mus.26191

Cited by 49 publications

(39 citation statements)

References 24 publications

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“…Deflazacort is a synthetic heterocyclic corticosteroid obtained by the fusion of methyloxazoline in the prednisone structure with great effectiveness and good tolerability. It causes less retention of sodium, has a strong anti-inflammatory action with immunosuppressive activity, low interference in carbohydrate metabolism and in the metabolism of calcium and phosphorus 49 .…”

Section: Deflazacort Versus Prednisonementioning

confidence: 99%

Duchenne muscular dystrophy: an historical treatment review

Werneck

Lorenzoni

Ducci

et al. 2019

Arq. Neuro-Psiquiatr.

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In this review, we discuss the therapies used in the treatment of patients with Duchenne muscular dystrophy since the first description of the disease. A short description is given of the various theories based on disease pathogenesis, which give the substrates for the many therapeutic interventions. A brief review of the methods of evaluation used in therapeutic trials is made. Of all the treatments, the only drugs that are still considered able to modify the course of the disease are the corticosteroids (prednisone/prednisolone/deflazacort). Other drugs (coenzyme Q10 and creatine) have had a little effect in a few functions without adverse reactions. Idebenone seems to improve the respiratory function in the long term. The trials with mRNA transcription, through nonsense mutations or exon 51 skipping, show some beneficial results in a few functional tests, but they are limited to a small set of DMD patients.

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Section: Deflazacort Versus Prednisonementioning

confidence: 99%

Duchenne muscular dystrophy: an historical treatment review

Werneck

Lorenzoni

Ducci

et al. 2019

Arq. Neuro-Psiquiatr.

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“…Steroids, a family of naturally-occurring secondary metabolites characterized by a four-fused ring structure, have exhibited a wide range of biological activities and have been shown to function as antitumoral, antiviral, antibacterial, and antioxidant agents [4]. The heterocyclic corticosteroid deflazacort (DFZ, Figure 1), an oxazoline-derivative of prednisolone, has been recently approved for the treatment of Duchenne dystrophy [5] showing high efficacy and good tolerability. In the frame of a study devoted to the development of a novel and convenient synthetic strategy for the preparation of DFZ, we recently found that a DFZ synthetic precursor called PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1), exhibited a good antibacterial activity against Staphylococcus aureus ATCC 29213 and Acinetobacter baumannii ATCC 17978 without showing cytotoxicity [6].…”

Section: Introductionmentioning

confidence: 99%

Steroid Derivatives as Potential Antimicrobial Agents against Staphylococcus aureus Planktonic Cells

et al. 2020

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In this work, the antibacterial activity of deflazacort and several of its synthetic precursors was tested against a panel of bacterial pathogens responsible for most drug-resistant infections including Staphylococcus aureus, Enterococcus spp., Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. The derivative of deflazacort, PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) showed the best antibacterial activity in a dose-dependent way. We focused on the action of PYED-1 against S. aureus cells. PYED-1 exhibited an additive antimicrobial effect with gentamicin and oxacillin against the methicillin-resistant S. aureus isolate 00717. In addition to its antimicrobial effect, PYED-1 was found to repress the expression of several virulence factors of S. aureus, including toxins encoded by the hla (alpha-haemolysin), hlb (beta-haemolysin), lukE-D (leucotoxins E-D), and sea (staphylococcal enterotoxin A) genes, and cell surface factors (fnbB (fibronectin-binding protein B) and capC (capsule biosynthesis protein C)). The expression levels of autolysin isaA (immunodominant staphylococcal antigen) were also increased.

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“…23 The posthoc analysis using the placebo arm from the trial studying another medication, Ataluren (discussed later), showed less mean decline from baseline to 48 weeks in the 6-minute walk test (6MWT), lower mean declines from baseline in the four-stair climb, and longer duration of ambulation in deflazacort-treated patients compared with prednisone/prednisolone-treated patients. 24 No significant differences were noticeable in the safety profiles; however, the deflazacort-treated group had a smaller mean increase in weight and BMI and a smaller mean increase in height.…”

Section: Duchenne Muscular Dystrophymentioning

confidence: 83%

Targeted Treatments for Inherited Neuromuscular Diseases of Childhood

et al. 2020

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In the past decade, the number of genes linked to neuromuscular diseases of childhood has expanded dramatically, and this genetic information is forming the basis for gene-specific and even mutation-specific therapies. At the forefront of these advances are the two recently approved treatments for spinal muscular atrophy: one, an antisense oligonucleotide that modifies splicing of the SMN2 gene, and, the other, a gene therapy vector that delivers the SMN1 gene to motor neurons, both of which are allowing patients to acquire developmental milestones previously unseen in this fatal disease. This review highlights these advances and emerging targeted therapies for Duchenne muscular dystrophy and centronuclear myopathy, while also covering enzyme replacement therapy and small molecule-based targeted therapies for conditions such as Pompe's disease and congenital myasthenic syndromes. With these and other newer techniques for targeted correction of genetic defects, such as CRISPR/Cas9, there is now hope that treatments for many more genetic diseases of the nervous system will follow in the near future.

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Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial

Abstract: This analysis, limited by its post hoc nature, suggests greater preservation of 6MWD and 4-stair climb with deflazacort vs. prednisone/prednisolone. A head-to-head comparison will better define these differences. Muscle Nerve 58: 639-645, 2018.

Cited by 49 publications

References 24 publications

Duchenne muscular dystrophy: an historical treatment review

Duchenne muscular dystrophy: an historical treatment review

Steroid Derivatives as Potential Antimicrobial Agents against Staphylococcus aureus Planktonic Cells

Targeted Treatments for Inherited Neuromuscular Diseases of Childhood

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