Helen Chao, Ph.D., Research Scientist
James D. Clelland, Ph.D., Research Scientist
Laura Panek, RN, Research Nurse
Laura Read, Ph.D., Research Scientist
Catherine L. Taylor Clelland, Visiting Research Scientist

Primary focus areas for the work of this Division are:

I. Novel large neutral amino acid treatments for movement disorders are developed with the patented technology of modulating the plasma pool of the large neutral amino acid precursors of amine neurotransmitters. There are three US and International patents issued to Dr. Richardson that have been licensed for manufacture and marketing by the New York State Office of Mental Health and the National Institutes of Health. The areas of concentration these three movement disorder patents are (1) the treatment of tardive dyskinesia with branched chain amino acids, (2) the treatment of secondary movement disorders with combinations of large neutral amino acids, and (3) the treatment of primary movement disorders with combinations of large neutral amino acids. One product is currently on the market and is being used in all three patent areas, and other products have been designed. This work has been funded by Federal grants and is currently supported by industrial grants and contracts. Relevant papers from this work are; "Efficacy of the Branched-Chain Amino Acids in the Treatment of Tardive Dyskinesia in Men", Am J Psychiatry 2003; 160:1117-1124 and "Branched Chain Amino Acid Treatment of Tardive Dyskinesia in Children and Adolescents", J Clin Psychiatry, 2004;65:92-96.

II. Diagnosis of psychiatric disorders and their vulnerability by gene screening of identified and discovered mutations and other sequence variants, coupled with tests of physiological function of the mutations. One of these novel mutations discovered is considered to be highly penetrant in schizophrenia. Ethnic differences have been seen in these findings. These data allowed us to develop targeted treatments for schizophrenia and bipolar disorder. There are two issued US patents currently supporting this work; the first for diagnosis of psychiatric disorders by specific sequence variants of the phenylalanine hydroxylase gene that we had discovered, and the second for the treatment of schizophrenia and bipolar disorder with the branched chain amino acids based on the physiological dysfunction found for mutations in these studies. The treatment product is now developed and tested. A licensee is being sought for these two patents for which Dr. Richardson is the Inventor and which she assigned to the New York State Office of Mental Health and the National Institutes of Health. This work has been supported by NIH grants and work is currently continued through the use of industrial contracts. A relevant paper for this work is; "Phenylalanine Hydroxylase Gene in Psychiatric Patients: Screening and Functional Assay of Mutations", Biol. Psychiatry, 2003:53:543-553.

III. This third area of work in a large sample of schizophrenics has demonstrated robust deficits in tetrahydrobiopterin (BH4) (the essential cofactor for the hydroxylation of the aromatic amino acids by phenylalanine hydroxylase [PAH], tyrosine hydroxylase [TH], and tryptophan hydroxylase [TPH]) in psychotic disorders. These findings have led to DNA sequence analysis of one of the genes related to the biosynthesis of the cofactor. and testing for functional changes related to discovered mutations. Analysis of one of these novel mutations suggested dysfunction in the metabolism of the amino acid, histidine in schizophrenia. Ethnic differences have been seen in these findings. This work has been supported by NIH grants and is currently supported by industrial contracts. This area of study links in with Section II above because of the interaction of BH4, BH4 synthesis pathway genes, phenylalanine and the phenylalanine hydroxylase gene.

IV. A fourth area of work is the conducting of genomics studies, which are designed to develop biological methods for the classification and monitoring of psychiatric and neurological illness including schizophrenia, bipolar disorder and Alzheimer's disease. The research projects in this area of research are based on the utilization of microarray technologies for simultaneous expression of measurements of thousands of different genes. These measurements are then analyzed using clustering algorithms, in order to determine classifying disease signatures. It is hoped that the biological classifications developed through these projects will become a clinically useful adjunct for current classification methods of psychiatric and neurological disease. These studies are being conducted with NIH funding in collaboration with the Mount Sinai School of Medicine, and the Institute for Aging and Dementia of the New York University School of Medicine

For further information, contact James Clelland at