title: A Potential Life-Threatening Reaction to Glatiramer Acetate in Rett Syndrome.
abstract: Rett syndrome is an X-linked dominant neurodevelopmental disorder manifesting with severe intellectual disability in females caused by various mutations in the MECP2 gene. Brain-derived neurotrophic factor (BDNF) is one of the main proteins regulated by the MECP2 protein; its overexpression in the MeCP2 mouse model partially corrects the Rett phenotype. Pharmacologic manipulations that lead to increased BDNF in individuals with Rett syndrome are expected to have a positive effect on the disorder. Glatiramer acetate, a well-known and safe multiple sclerosis immune modulator, increases BDNF levels in multiple sclerosis animal models and patients responding to treatment, as well as in Rett mouse models.
  
  
  
  Fourteen patients with mutation-proven Rett syndrome were recruited for a clinical trial with glatiramer acetate. Baseline data and follow-up data were collected during the trial, which had to be stopped because of a severe adverse event. Our objective is to describe this unexpected potentially life-threatening event in response to glatiramer in patients with Rett syndrome.
  
  
  
  Four of 14 patients with Rett syndrome who were recruited and treated with daily injections of glatiramer acetate as part of an open-label clinical trial developed an exaggerated immediate postinjection response, which was experienced as life threatening in three of the patients, necessitating arrest of the trial.
  
  
  
  Despite the known safety profile of glatiramer acetate in adult and pediatric patients with multiple sclerosis, its use in Rett syndrome should be cautiously reconsidered. The described severe adverse event can be related to these patients' primary autonomic nervous system dysfunction.
authors.affiliation: The Service for Rare Disorders, Edmond and Lilly Safra Pediatric Hospital, Sheba Medical Center, Tel Ha Shomer, Israel; Pediatric Neurology Unit, Edmond and Lilly Safra Pediatric Hospital, Sheba Medical Center, Tel Ha Shomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Andreea
authors.initials: A
authors.lastname: Nissenkorn
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Allergy Unit, Edmond and Lilly Safra Pediatric Hospital, Sheba Medical Center, Tel Ha Shomer, Israel.
authors.forename: Mona
authors.initials: M
authors.lastname: Kidon
authors.affiliation: Pediatric Neurology Unit, Edmond and Lilly Safra Pediatric Hospital, Sheba Medical Center, Tel Ha Shomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; The National Rett Center, Edmond and Lilly Safra Pediatric Hospital, Sheba Medical Center, Tel Ha Shomer, Israel. Electronic address: Bruria.BenZeev@sheba.health.gov.il.
authors.forename: Bruria
authors.initials: B
authors.lastname: Ben-Zeev
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use / Q000633:toxicity*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use / Q000633:toxicity*; D007267:Injections; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D015518:Rett Syndrome / Q000188:drug therapy* / Q000235:genetics; D065566:Subcutaneous Absorption; D017211:Treatment Failure
chemical_list: D007155:Immunologic Factors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D000068717:Glatiramer Acetate
keywords: MECP2; autonomic nervous system; brain-derived neurotrophic factor (BDNF); immediate postinjection response (IPIR)