Creatine transporter deficiency is a metabolic disorder characterized by
intellectual disability, autistic-like behaviour and
epilepsy. There is currently no cure for
creatine transporter deficiency, and reliable
biomarkers of translational value for monitoring
disease progression and response to
therapeutics are sorely lacking. Here, we found that mice lacking functional
creatine transporter display a significant alteration of neural oscillations in the EEG and a severe epileptic phenotype that are recapitulated in patients with
creatine transporter deficiency. In-depth examination of knockout mice for
creatine transporter also revealed that a decrease in EEG theta power is predictive of the manifestation of spontaneous
seizures, a frequency that is similarly affected in patients compared to healthy controls. In addition, knockout mice have a highly specific increase in haemodynamic responses in the cerebral cortex following sensory stimuli. Principal component and Random Forest analyses highlighted that these functional variables exhibit a high performance in discriminating between pathological and healthy phenotype. Overall, our findings identify novel, translational and non-invasive
biomarkers for the analysis of brain function in
creatine transporter deficiency, providing a very reliable protocol to longitudinally monitor the efficacy of potential therapeutic strategies in preclinical, and possibly clinical, studies.