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.
Competing Interests: Declaration of competing interest Aloise Mabondzo reports financial support was provided by Ceres Brain Therapeutics. Aloise Mabondzo reports a relationship with Ceres Brain Therapeutics that includes: consulting or advisory and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Anne-Cécile Guyot reports financial support was provided by Ceres Brain Therapeutics. Anne-Cecile Guyot reports a relationship with Ceres Brain Therapeutics that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Clara Lhotellier reports financial support was provided by Ceres Brain Therapeutics. Clara Lhotellier reports a relationship with Ceres Brain Therapeutics that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Clémence Disdier reports financial support was provided by Ceres Brain Therapeutics. Clemence Disdier reports a relationship with Ceres Brain Therapeutics that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Thomas Joudinaud reports financial support was provided by Ceres Brain Therapeutics. Thomas Joudinaud reports a relationship with Ceres Brain Therapeutics that includes: consulting or advisory and equity or stocks. Thomas Joudinaud has patent pending to Assignee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Henri Benech reports a relationship with Ceres Brain Therapeutics that includes: employment and equity or stocks. Henri Benech has patent pending to Assignee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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