Dodecyl creatine ester, a promising treatment to deliver creatine to neurons, achieves pharmacology efficacy in creatine transporter deficiency.

Dodecyl creatine ester (DCE) is a creatine prodrug currently developed for brain diseases, including creatine transporter deficiency (CTD), an incurable rare genetic disease. A dual strategy combining a prodrug to bypass the non-functional creatine transporter and its delivery via the nose-to-brain pathway has been proposed to replenish creatine levels in cerebral cells, particularly in neurons of CTD patients. In vitro and in vivo studies in various animal models, including wild-type non-human primates and creatine transporter deficient mice, show that formulated DCE, when administered intranasally, achieves significant cerebral distribution up to the target cells, the neurons, and modulates the expression of neuronal markers related to cognitive function at doses intended for patients. These compelling results contribute to a better understanding of the pharmacokinetics and pharmacodynamics of DCE after nasal administration, with a particular focus on the crucial role of the nose-to-brain pathway in DCE distribution.