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Steroid Responsiveness in Duchenne Muscular Dystrophy – Predictive Value of Epigenetic Regulator Histone Deacetylase 2

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Abstract

Objective

To find the role of an epigenetic regulator histone deacetylase (HDAC-2) in predicting steroid responsiveness in patients with Duchenne muscular dystrophy (DMD).

Methods

Peripheral blood mononuclear cells were isolated from three milliliters of venous blood sample of patients with DMD for estimation of HDAC-2 levels. The patients were then given prednisolone at 0.75 mg/kg/d and followed up for response. Improvement in muscle power and timed function tests were evaluated 2 monthly for 6 mo. Side- effects of steroids were also noted.

Results

HDAC-2 values showed a linear correlation with improvement in muscle power at 6 mo as reflected in direct assessment and in various functional tests. When ≥3 point change from baseline was considered in power of various muscle groups at 6 mo as cut off to distinguish good responders (GR) from poor responders (PR) of steroid, a HDAC-2 value of ≥4.40 seemed to be 92.6% sensitive and 100% specific to distinguish GRs.

Conclusions

The degree of improvement in power and various timed function tests at 6 mo could be predicted from the HDAC-2 value of the individual patient recorded at baseline. HDAC-2 levels at baseline might be a good biomarker for predicting steroid response in patients with DMD.

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Acknowledgements

The authors would like to acknowledge Thermo Fisher Scientific Inc., Bartlesville, OK, USA and Roche Diagnostics, Indianapolis, IN, USA for providing kits for measuring HDAC-2 and doing PCR.

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Authors and Affiliations

  1. Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India

    Sunil Pradhan & Animesh Das

  2. Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

    Harshit Singh, Saurabh Chaturvedi, Kritika Singh, Ravi Mishra, Durga Prassana Misra & Vikas Agarwal

Authors
  1. Sunil Pradhan
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  2. Animesh Das
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  3. Harshit Singh
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  4. Saurabh Chaturvedi
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  5. Kritika Singh
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  6. Ravi Mishra
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  7. Durga Prassana Misra
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  8. Vikas Agarwal
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Contributions

SP, VA and DPM designed the study. AD collected the data, managed the patients and wrote the manuscript. HS, SC, KS and RM did the HDAC-2 analysis and provided technical help. SP is the guarantor for this paper.

Corresponding author

Correspondence to Sunil Pradhan.

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Source of Funding

This work received support partially from Intramural Grant (PGI/DIR/RC/607/2016) of Sanjay Gandhi Post Graduate Institute of Medical Sciences, and partially from Council of Science and Technology grant, Uttar Pradesh, India (CST/SEPRD/D-5052).

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Pradhan, S., Das, A., Singh, H. et al. Steroid Responsiveness in Duchenne Muscular Dystrophy – Predictive Value of Epigenetic Regulator Histone Deacetylase 2. Indian J Pediatr 87, 692–698 (2020). https://doi.org/10.1007/s12098-020-03183-5

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  • DOI: https://doi.org/10.1007/s12098-020-03183-5

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