OP23 – 2759: Pharmacological treatment of Rett syndrome with glatiramer acetate (Copaxone)

Background Glatiramer Acetate (GA) represents a collection of synthetic polypeptides approved for the treatment of relapsing–remitting multiple sclerosis, for patients who are 18 years or older. Its high safety profile has been documented in large cohorts of patients 10 or older. Quantitative immunofluorescence assays showed about twofold increase in neuronal expression of BDNF following GA treatment. It causes elevation of BDNF expression up to the level in naive control mice in several cortical areas in the Mecp2 mutated mouse brain. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression (Chang et al. 2006). Objective Increase in BDNF levels, caused by GA administration will lead to amelioration of RTT related symptoms. Hypothesis: The experimental treatment will be well tolerated and result in at least 20% improvement in at least one of the Rett syndrome related symptoms. Methods Study design: Phase II, dose-escalating trial. Inclusion criteria Female, ambulatory patients with genetically confirmed RTT who are 10 or more years old. Outcome measures: Gait, respiratory function, attention and memory, EEG. Objectives • Primary: To assess primary efficacy of GA in improving gait speed in patients with RTT. • Secondary: a. To evaluate secondary efficacy of GA in improving cognition (visual attention, memory and visual pursuit), autonomic (respiratory) function, encephalopathy (EEG), and quality of life. b. To assess safety and maximally tolerated dosage. Results Treatment with GA lead to significant improvement in gait speed, breath hold index and recognition memory. Seven of 10 treated girls exhibited the improvement. There was no difference in age, genetic status or Rett syndrome severity scores between those who did and who did not improve. Conclusion Treatment with GA was well-tolerated and lead to significant improvements in girls with RTT.