The Quest for the Prediction of Steroid Responsiveness in Duchenne Muscular Dystrophy
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EDITORIAL COMMENTARY
The Quest for the Prediction of Steroid Responsiveness in Duchenne Muscular Dystrophy Renu Suthar 1 & Jitendra Kumar Sahu 1 Received: 23 May 2020 / Accepted: 3 June 2020 # Dr. K C Chaudhuri Foundation 2020
Duchenne muscular dystrophy (DMD), first described in 1834, is a progressive and crippling muscle disease. With an improvement in supportive care, the life span of boys with DMD has increased significantly, but the quality of life remains suboptimal. Glucocorticoids, an approved therapy for boys with DMD, improve muscle strength, lengthen the duration of independent ambulation, postpone the onset of cardiomyopathy, improve pulmonary function, and decrease the incidence of scoliosis [1]. The mechanism of action of glucocorticoid therapy in DMD is not fully elucidated, and there are several proposed mechanisms like anti-inflammatory, membrane stabilization, differentiation of epigenetic regulators in muscle fibers etc. Long term steroid use is associated with significant adverse effects [2]. The concern for adverse effects among the parents and physicians is so much that more than 50% of boys with DMD do not receive optimum steroids therapy despite being the standard of care. Pradhan and colleagues studied the levels of histone deacetylase-2 (HDAC-2) in boys with DMD receiving prednisolone at 0.75 mg/kg/d for six months and reported that high baseline HDAC-2 levels correlated with good steroid response [3]. The results of this study are interesting and relevant in elucidating the mechanism of steroid responsiveness in boys with DMD. The variable response to steroid therapy is well known in boys with DMD. The most important predictor of disease course is the nature of the genetic defect in the dystrophin gene. The most plausible explanation is the reading frame rule, whereas the deletions causing disruption of reading frame and premature truncation of dystrophin protein are often associated with a more severe phenotype. Another predictor for steroid responsiveness is the baseline functional abilities of
the child. Six-minute walk test (6MWT), a global muscle and cardiorespiratory functions indicator, is a reliable and universally accepted outcome measure in boys with DMD. The trajectories of 6-min walk distance at baseline predict future course of the disease in boys with DMD; 4.4 at baseline in boys with DMD can predict good steroid responsiveness [3]. Limitations in the clinical application of HDAC2 assessment at baseline in boys with DMD are obvious, with the availability of the testing facility and increase in the cost of the care. The other interesting application of increased HADC-2 expression in peripheral blood leucocytes in boys with DMD, as observed by Pradhan and colleagues, could serve as a surrogate marker of HDAC-2 expression in skeletal muscles.
* Jitendra Kumar Sahu [email protected]
References
1
Compliance with Ethical Standards Conflict of Interest None.
1. Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chan
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