The role of the creatine transporter (CrT) in the brain is still not fully understood. From patient and animal data, it is clear that the CrT is required for creatine to get into the brain. Presumably, the CrT brings creatine into the brain across the blood brain barrier, and loss of the CrT prevents creatine entry into the brain. However, there are still unanswered questions that require further study to support this hypothesis. For example, in patients with creatine synthesis disorders, why does it take very high doses of creatine for an extended period of time to achieve significant brain creatine levels? In addition, it has been shown that creatine synthesis enzymes are expressed in the brain, suggesting that the brain may be able to make creatine.
In order to better understand how neurons acquire creatine, we are utilizing mice that lack CrT only at the blood-brain barrier. These data studies will significantly affect the design of treatments for CTD and other creatine deficiencies.