Complessi di fosfocreatina
Despite the amount of favorable evidence, the use of creatine as a medicinal drug in diseases of the central nervous system is still unsatisfactory. Certainly, one of the problems is the very limited bioavailability of creatine to the brain. Creatine is a very polar molecule, and as such it crosses with difficulty the blood-brain barrier. In our laboratory we showed that even very high doses of creatine enter the brain very little when administered systemically (Perasso et al., 2003). The marked polarity of creatine is overcome in mammals by a transporter that carries this molecule across the blood-brain barrier. However, transport by this carrier is very slow, moreover there are hereditary conditions where the transporter is missing or malfunctioning. Creatine-derived molecules that could duplicate the effects of creatine while crossing the blood-brain barrier and neuronal plasma membrane in a carrier-independent way would represent a major progress in the therapy of either (1) acute neurological conditions like stroke, (2) chronic neurological conditions like neurodegenerative diseases, or (3) hereditary neurological diseases like creatine transporter deficiency. The latter condition qualifies for the status of “orphan disease”. We invented molecules based on phosphocreatine that can both (1) cross biological membranes independently of the creatine carrier and (2) reproduce known neuroprotective effects of creatine against anoxia. An example of these molecules is phosphocreatine-Mg-complex acetate. We trust that this and similar molecules will be used in the therapy of both rare diseases like creatine transporter deficiency (an “orphan” disease) and more widespread diseases like stroke and other diseases where neuronal energetic metabolism is compromised.