METHODS FOR KYNURENINE SYSTEM IN HUNTINGTON'S DISEASE

PROTOTYPE MULTIPLE ELECTRODE LIQUID CHROMATOGRAPHY (N-ELC) SYSTEMS HAVE BEEN DEVELOPED FOR SIMULTANEOUS ANALYSIS OF SEVERAL HUNDRED COMPONENTS IN BIOLOGICAL SAMPLES AT THE FEMTOGRAM LEVEL. A MAJOR MARKET FOR N-ELC SYSTEMS DEPENDS ON THE DEMONSTRATION OF THE RELEVANCE OF MULTICOMPONENT MEASUREMENTS TO DEGENERATIVE NEUROLOGICAL DISORDERS. RECENTLY, QUINOLINIC ACID (QA) HAS BEEN SHOWN TO REPLICATE THE HISTOLOGICAL AND NEUROCHEMICAL FEATURES OF HUNTINGTON'S DISEASE (HD), A PROGRESSIVE DEGENERATIVE NEUROLOGICAL DIS- ORDER. ESA WILL DEVELOP AND APPLY N-ELC METHODS FOR THE ANALYSIS OF THE KYNURENINE (KY) PATHWAY LEADING TO THE QA. THE INTENT IS TO DEVELOP PROCEDURES CAPABLE OF LOCATING A METABOLIC DEFECT IN HD LEADING TO INCREASED QA ACCUMULATION.SIMULTANEOUSLY, THE N-ELC PROCEDURES WILL PROVIDE INFORMA- TION ON THE APPROXIMATELY 40 OTHER COMPONENTS OF THE TYROSINE AND TRYPTOPHAN PATHWAYS. THESE DATA WILL BE USED TO QUALIFY THE KY PATHWAY AND IMPROVE INTERCLASS CORRELA- TIONS BETWEEN HD AND NORMALS. AS PART OF AN ONGOING PROGRAMAT MGH, THE SAMPLES WILL ALSO BE ASSAYED FOR QA, AMINO ACIDS, AND NEUROPEPTIDES. THE LONG-RANGE AIM OF THE PROJECTIS TO DEFINE THE NEUROCHEMICAL PATHWAYS IN HD IN SUFFICIENT DETAIL TO GUIDE PHARMACOLOGICAL INTERVENTION.