Introduction

Di-acetyl creatine ethyl ester (DAC) is an innovative compound, a precursor of creatine that crosses biological membranes independently of the creatine transporter, providing a cure for the rare hereditary disease induced by the lack of such a transporter.

Technical features

Creatine is fundamental in the energy metabolism of the brain. The rare disease caused by the genetic deficiency of the creatine transporter causes severe neurological symptoms, and cannot be cured as creatine crosses biological membranes only with the help of its transporter. Thus, we designed and synthesized di-acetyl creatine ethyl ester (DAC), a compound that crosses biological membranes independently of the transporter due to its high lipophilicity. We have demonstrated its ability to increase intracellular creatine levels even after the creatine transporter is blocked and to counteract the cellular damage induced by transporter blockage. In our experiments after blocking the creatine transporter, the DAC was able both to prevent synaptic transmission deficiency and to increase intracellular creatine.

Possible Applications

• Treatment of creatine transporter deficiency, a rare disease currently incurable;
• Coadjuvant in energy deficiency diseases such as cerebral ischemic stroke.

Advantages

• Possibility of using the compound even in the absence of the creatine transporter;
• Increase in creatine levels in the body;
• Possibility to counteract the neuronal damage induced by the blockage of the transporter.