CREATINE ADMINISTRATION IN CREATINE DEFICIENCY SYNDROMES

Some genetic conditions cause widespread brain damage in newborns and infants by preventing the ability of the brain to synthesize creatine. Administration of creatine by mouth can replenish the brain store of this compound. However, orally administered creatine crosses poorly the barrier that normally exists between the blood and the brain (the so-called blood-brain barrier), thus replenishing is slow and full recovery is not usually achieved. This project was designed to investigate whether or not parenteral injection of creatine could cause a faster or greater accumulation of this compound into the brain. The rationale was that parenteral administration of creatine results in higher blood levels of this compound, thus it may cross faster the blood-brain barrier. However, the results showed that even after parenteral injection the accumulation of creatine into the brain is slow, because of the extreme difficulty with which this compound enters the brain. This result shows that the easiest possible way of improving creatine crossing of the blood-brain barrier (parenteral administration) would probably be of limited usefulness to creatine-deficient patients. It points out to the need for more complex and sophisticated ways to improve brain avalability of creatine. These may include modifying the molecule of creatine, or attaching it to other molecules (called "carriers") in order to have it cross better the blood-brain barrier. This is the research we plan to do to improve therapy of creatine-deficiency syndromes.