A potential life threatening reaction to Glatiramer acetate in Rett syndrome

Publication date: Available online 7 December 2016
Source:Pediatric Neurology
Author(s): Andreea Nissenkorn, Mona Kidon, Bruria Ben-Zeev
Background and objectivesRett 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; it`s over expression in the MeCP2 mouse model partially correct the Rett phenotype. Pharmacological manipulations that will lead to increased BDNF in Rett patients are expected to have a positive effect on the disorder. Glatiramer acetate, a well-known and safe multiple sclerosis immune modulator, which also increases BDNF levels in multiple sclerosis animal models and treatment responding patients, as well as in Rett mouse model. Based on it`s safety profile was approved for a clinical trial in MECP2 positive Rett patients leading to a designed clinical trial. Our objective is to describe an unexpected potential life threatening event to glatiramer in patients with Rett syndrome.Results4 out of 14 patients with Rett syndrome that were recruited and treated with daily injections of Glatiramer acetate as part of an open label clinical trial developed an exaggerated immediate post injection response (IPIR) which was experienced as life threatening in 3 of the patients necessitating arrest of the trial .ConclusionDespite the known safety profile of Glatiramer acetate in adult and pediatric patients with multiple sclerosis its use in Rett syndrome should be cautiously re-considered. The described severe adverse event can be related to these patients' primary autonomic nervous system dysfunction.



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