PMID- 28254244 OWN - NLM STAT- MEDLINE DCOM- 20171218 LR - 20180913 IS - 1873-5150 (Electronic) IS - 0887-8994 (Linking) VI - 68 DP - 2017 Mar TI - A Potential Life-Threatening Reaction to Glatiramer Acetate in Rett Syndrome. PG - 40-43 LID - S0887-8994(16)30821-9 [pii] LID - 10.1016/j.pediatrneurol.2016.11.006 [doi] AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Nissenkorn, Andreea AU - Nissenkorn A AD - 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. FAU - Kidon, Mona AU - Kidon M AD - 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. FAU - Ben-Zeev, Bruria AU - Ben-Zeev B AD - 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. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161207 PL - United States TA - Pediatr Neurol JT - Pediatric neurology JID - 8508183 RN - 0 (Immunologic Factors) RN - 0 (MECP2 protein, human) RN - 0 (Methyl-CpG-Binding Protein 2) RN - 5M691HL4BO (Glatiramer Acetate) SB - IM MH - Adolescent MH - Child MH - Female MH - Glatiramer Acetate/therapeutic use/*toxicity MH - Humans MH - Immunologic Factors/therapeutic use/*toxicity MH - Injections MH - Methyl-CpG-Binding Protein 2/genetics MH - Rett Syndrome/*drug therapy/genetics MH - Subcutaneous Absorption MH - Treatment Failure OTO - NOTNLM OT - MECP2 OT - autonomic nervous system OT - brain-derived neurotrophic factor (BDNF) OT - immediate postinjection response (IPIR) EDAT- 2017/03/04 06:00 MHDA- 2017/12/19 06:00 CRDT- 2017/03/04 06:00 PHST- 2016/10/13 00:00 [received] PHST- 2016/11/23 00:00 [accepted] PHST- 2017/03/04 06:00 [pubmed] PHST- 2017/12/19 06:00 [medline] PHST- 2017/03/04 06:00 [entrez] AID - S0887-8994(16)30821-9 [pii] AID - 10.1016/j.pediatrneurol.2016.11.006 [doi] PST - ppublish SO - Pediatr Neurol. 2017 Mar;68:40-43. doi: 10.1016/j.pediatrneurol.2016.11.006. Epub 2016 Dec 7.