NMDA-BASED TREATMENT OF SCHIZOPHRENIA

Schizophrenia is a major mental disorder with estimated prevalence of 1 percent of the population. Current treatment approaches for schizophrenia rely on the use of dopamine antagonists (antipsychotics). These drugs have only partial effectiveness in a large percentage of patients, especially in the treatment of negative and cognitive symptoms. This project will explore alternative treatment strategies for schizophrenia based upon the PCP model of the disorder. PCP (phencyclidine, "angel dust") induces symptoms that closely resemble those of schizophrenia, by blocking neurotransmission mediated at N-methyl-D-aspartate (NMDA) type glutamate receptors. Several dietary amion acids, including glycine and D-serine, potentiate activation of NMDA receptors in vitro and reverse behavioral effects of PCP in vivo. In small scale clinical trials, glycine and D-serine have been shown to be effective in the treatment of persistent symptoms of schizophrenia. This project will focus on development of commercializable formulations of glycine and D-serine. Both products fall within the scope of Federal medical foods legislation. The specific aims are to explore feasibility of glycine and D-serine development as medical foods for dietary management of schizophrenia. In the case of D-serine, preclinical toxicology would be required. In successful, this project will lead to development of new treatment approaches for schizophrenia.