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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autistic Disorder / drug therapy
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Autistic Disorder / etiology*
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Blood-Brain Barrier
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Brain Diseases, Metabolic, Inborn / complications
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Brain Diseases, Metabolic, Inborn / drug therapy*
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Cerebrovascular Circulation / drug effects
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Cognition Disorders / drug therapy
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Cognition Disorders / etiology*
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Creatine / deficiency*
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Creatinine / analogs & derivatives*
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Creatinine / therapeutic use
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Disease Models, Animal
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Electroencephalography
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Epilepsy / drug therapy
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Epilepsy / etiology*
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Hemodynamics / drug effects
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Male
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Mental Retardation, X-Linked / complications
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Mental Retardation, X-Linked / drug therapy*
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Mice
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Mice, Inbred C57BL
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Phenotype
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Plasma Membrane Neurotransmitter Transport Proteins / deficiency*
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Seizures / drug therapy
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Seizures / etiology
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Stereotyped Behavior / drug effects
Substances
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Plasma Membrane Neurotransmitter Transport Proteins
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cyclocreatine
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Creatinine
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Creatine
Supplementary concepts
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Creatine deficiency, X-linked