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

F. Cacciante; M. Gennaro; G. Sagona; R. Mazziotti; L. Lupori; E. Cerri; E. Putignano; M. Butt; M.-H.T. Do; J.C. McKew; M.G. Alessandrì; R. Battini; G. Cioni; T. Pizzorusso; L. Baroncelli

doi:10.1038/s41598-020-75436-4

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

F. Cacciante, M. Gennaro, G. Sagona, R. Mazziotti, L. Lupori, E. Cerri, E. Putignano, M. Butt, M.-H.T. Do, J.C. McKew, M.G. Alessandrì, R. Battini, G. Cioni, T. Pizzorusso, L. Baroncelli

Fondazione Stella Maris

Research output: Contribution to journal › Article › peer-review

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. © 2020, The Author(s).

Original language	English
Journal	Sci. Rep.
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-75436-4
Publication status	Published - 2020

Keywords

creatine
creatinine
cyclocreatine
plasma membrane neurotransmitter transporter
animal
autism
blood brain barrier
brain circulation
C57BL mouse
cognitive defect
complication
disease model
drug effect
electroencephalography
epilepsy
hemodynamics
male
metabolic encephalopathy
mouse
phenotype
seizure
stereotypy
X linked mental retardation
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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10.1038/s41598-020-75436-4

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85094098115&doi=10.1038%2fs41598-020-75436-4&partnerID=40&md5=4a1b0571b6a9179c8ad8bfdc1c3b1d2e

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Cacciante, F., Gennaro, M., Sagona, G., Mazziotti, R., Lupori, L., Cerri, E., Putignano, E., Butt, M., Do, M-HT., McKew, J. C., Alessandrì, M. G., Battini, R., Cioni, G., Pizzorusso, T., & Baroncelli, L. (2020). Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency: Scientific Reports. Sci. Rep., 10(1). https://doi.org/10.1038/s41598-020-75436-4

Cacciante, F, Gennaro, M, Sagona, G, Mazziotti, R, Lupori, L, Cerri, E, Putignano, E, Butt, M, Do, M-HT, McKew, JC, Alessandrì, MG , Battini, R , Cioni, G, Pizzorusso, T & Baroncelli, L 2020, 'Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency: Scientific Reports', Sci. Rep., vol. 10, no. 1. https://doi.org/10.1038/s41598-020-75436-4

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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. {\textcopyright} 2020, The Author(s).",

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author = "F. Cacciante and M. Gennaro and G. Sagona and R. Mazziotti and L. Lupori and E. Cerri and E. Putignano and M. Butt and M.-H.T. Do and J.C. McKew and M.G. Alessandr{\`i} and R. Battini and G. Cioni and T. Pizzorusso and L. Baroncelli",

note = "Cited By :1 Export Date: 19 March 2021 Correspondence Address: Baroncelli, L.; Institute of Neuroscience, Via Moruzzi 1, Italy; email: baroncelli@in.cnr.it",

year = "2020",

doi = "10.1038/s41598-020-75436-4",

language = "English",

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T1 - Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

T2 - Scientific Reports

AU - Cacciante, F.

AU - Gennaro, M.

AU - Sagona, G.

AU - Mazziotti, R.

AU - Lupori, L.

AU - Cerri, E.

AU - Putignano, E.

AU - Butt, M.

AU - Do, M.-H.T.

AU - McKew, J.C.

AU - Alessandrì, M.G.

AU - Battini, R.

AU - Cioni, G.

AU - Pizzorusso, T.

AU - Baroncelli, L.

N1 - Cited By :1 Export Date: 19 March 2021 Correspondence Address: Baroncelli, L.; Institute of Neuroscience, Via Moruzzi 1, Italy; email: baroncelli@in.cnr.it

PY - 2020

Y1 - 2020

N2 - 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. © 2020, The Author(s).

AB - 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. © 2020, The Author(s).

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KW - creatinine

KW - cyclocreatine

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KW - brain circulation

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KW - drug effect

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KW - hemodynamics

KW - male

KW - metabolic encephalopathy

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KW - Autistic Disorder

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KW - Electroencephalography

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KW - Mice, Inbred C57BL

KW - Phenotype

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KW - Seizures

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DO - 10.1038/s41598-020-75436-4

M3 - Article

SN - 2045-2322

VL - 10

JO - Sci. Rep.

JF - Sci. Rep.

IS - 1

ER -

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

Abstract

Keywords

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