Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Cacciante, Francesco;Lupori, Leonardo;Putignano, Elena;Cioni, Giovanni;Pizzorusso, Tommaso;Baroncelli, Laura
2020

Abstract

Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.
Settore BIO/09 - Fisiologia
animals; autistic disorder; blood-brain barrier; brain diseases, metabolic, inborn; cerebrovascular circulation; cognition disorders; creatine; creatinine; disease models, animal; electroencephalography; epilepsy; hemodynamics; male; mental retardation, X-linked; mice; mice, inbred C57BL; phenotype; plasma membrane neurotransmitter transport proteins; seizures; stereotyped behavior
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11384/124363
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