Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate

Aleksandra Djukic, Roee Holtzer, Shlomo Shinnar, Hiren Muzumdar, Susan A. Rose, Wenzhu Bi Mowrey, Aristea S. Galanopoulou, Ruth Shinnar, Jeffrey J. Jankowski, Judith F. Feldman, Sophia Pillai, Solomon L. Moshe

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 4 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.

Original languageEnglish (US)
JournalPediatric Neurology
DOIs
StateAccepted/In press - Feb 27 2016

Fingerprint

Rett Syndrome
Gait
Brain
Therapeutics
Quality of Life
Breath Holding
Nonparametric Statistics
Reproducibility of Results
Cognition
Glatiramer Acetate
Outcome Assessment (Health Care)

Keywords

  • Clinical trial
  • Gait
  • Glatiramer acetate
  • Rett syndrome

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Cite this

Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate. / Djukic, Aleksandra; Holtzer, Roee; Shinnar, Shlomo; Muzumdar, Hiren; Rose, Susan A.; Mowrey, Wenzhu Bi; Galanopoulou, Aristea S.; Shinnar, Ruth; Jankowski, Jeffrey J.; Feldman, Judith F.; Pillai, Sophia; Moshe, Solomon L.

In: Pediatric Neurology, 27.02.2016.

Research output: Contribution to journalArticle

Djukic, Aleksandra ; Holtzer, Roee ; Shinnar, Shlomo ; Muzumdar, Hiren ; Rose, Susan A. ; Mowrey, Wenzhu Bi ; Galanopoulou, Aristea S. ; Shinnar, Ruth ; Jankowski, Jeffrey J. ; Feldman, Judith F. ; Pillai, Sophia ; Moshe, Solomon L. / Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate. In: Pediatric Neurology. 2016.
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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 4 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.",
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AU - Rose, Susan A.

AU - Mowrey, Wenzhu Bi

AU - Galanopoulou, Aristea S.

AU - Shinnar, Ruth

AU - Jankowski, Jeffrey J.

AU - Feldman, Judith F.

AU - Pillai, Sophia

AU - Moshe, Solomon L.

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