Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate

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.