2. Academic Validation
  3. Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

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

  • Sci Rep. 2020 Oct 27;10(1):18361. doi: 10.1038/s41598-020-75436-4.
Francesco Cacciante 1 2,  Mariangela Gennaro 1,  Giulia Sagona 3 4,  Raffaele Mazziotti 1,  Leonardo Lupori 2,  Elisa Cerri 1,  Elena Putignano 1,  Mark Butt 5,  Minh-Ha T Do 6,  John C McKew 6,  Maria Grazia Alessandrì 4,  Roberta Battini 4 7,  Giovanni Cioni 4 7,  Tommaso Pizzorusso 1 3,  Laura Baroncelli 8 9
Affiliations

Affiliations

  • 1 Institute of Neuroscience, National Research Council (CNR), Via Moruzzi 1, 56124, Pisa, Italy.
  • 2 BIO@SNS Lab, Scuola Normale Superiore di Pisa, 56125, Pisa, Italy.
  • 3 Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, 50135, Florence, Italy.
  • 4 Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128, Pisa, Italy.
  • 5 Tox Path Specialists, Frederick, MD, 21701, USA.
  • 6 Lumos Pharma, Austin, TX, 78756, USA.
  • 7 Department of Clinical and Experimental Medicine, University of Pisa, 56126, Pisa, Italy.
  • 8 Institute of Neuroscience, National Research Council (CNR), Via Moruzzi 1, 56124, Pisa, Italy. baroncelli@in.cnr.it.
  • 9 Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128, Pisa, Italy. baroncelli@in.cnr.it.
PMID: 33110151 DOI: 10.1038/s41598-020-75436-4
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.

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