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Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate

  • Aleksandra Djukic
    Correspondence
    Communications should be addressed to: Dr. Djukic; Saul R. Korey Department of Neurology; Albert Einstein College of Medicine; 3351 Steuben Avenue; Bronx, NY 10467.
    Affiliations
    Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York

    Rett Syndrome Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

    Department of Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
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  • Roee Holtzer
    Affiliations
    Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York

    Ferkauf Graduate School of Psychology of Yeshiva University, Bronx, New York
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  • Shlomo Shinnar
    Affiliations
    Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York

    Rett Syndrome Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

    Department of Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
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  • Hiren Muzumdar
    Affiliations
    Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania
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  • Susan A. Rose
    Affiliations
    Department of Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
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  • Wenzhu Mowrey
    Affiliations
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
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  • Aristea S. Galanopoulou
    Affiliations
    Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York

    Rett Syndrome Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

    Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York
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  • Ruth Shinnar
    Affiliations
    Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York
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  • Jeffrey J. Jankowski
    Affiliations
    Department of Social Sciences, Queensborough Community College, City University of New York, Bayside, New York
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  • Judith F. Feldman
    Affiliations
    Department of Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
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  • Sophia Pillai
    Affiliations
    Department of Pediatrics, Weill Cornell Medical College, New York, New York
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  • Solomon L. Moshé
    Affiliations
    Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York

    Rett Syndrome Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

    Department of Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

    Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York
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      Abstract

      Background

      Rett syndrome (RTT) is a severe neurological disease that primarily affects females. The level of brain derived neurotropic factor (BDNF) expression directly correlates with the severity of RTT related symptoms. Because Glatiramer acetate (GA) stimulates secretion of BDNF in the brain, we conducted the study with the objective to assess its efficacy in improving gait velocity cognition, respiratory function, electroencephalographic findings, and quality of life in patients with RTT.

      Methods

      Phase two, open label, single center trial. Inclusion criteria: ambulatory girls with genetically confirmed RTT, 10 years or older. Pre- and post-treatment measures were compared using the non-parametric Wilcoxon signed rank sum test and paired t-tests.

      Results

      Ten patients were enrolled and completed the trial. Gait velocity improved significantly (improvement range 13%-95%, p=0.03 for both tests) and emerged as an especially valuable outcome measure with excellent test- retest reliability of the 2 trials within sessions (intraclass correlation coefficient=0.94). Memory, and the breath holding index also improved significantly (p≤0.03). Epileptiform discharges decreased in all four patients who had them at baseline. There was a trend towards improved quality of life, which did not reach statistical significance.

      Conclusions

      This prospective open-label trial provides important preliminary information related to the efficacy of GA in improving gait velocity in female patients with RTT who are 10 years or older. The results of this trial justify the need for larger scale controlled trials of GA as well as provide a template for assessing the efficacy of other interventions in RTT.

      Keywords

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