Methods for Kynurenine System in Huntington's Disease

Matson, Wayne

Abstract

Prototype Multiple Electrode Liquid Chromatogrampy (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 disorder. We propose to develop and apply n-ELC methods for the analysis of the kynurenine (KY) pathway leading to 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 information on approximately 40 other components of the tyrosine and tryptophan pathways. These data will be used to qualify the KY pathway and improve interclass correlations between HD and normals. The measurements will be carried out on CSF from Massachusetts General Hospital, Boston, MA (MGH) and brain tissue from the McLean Hospital Brain Tissue Resource Center, Belmont, MA. As part of an ongoing program at MGH, the samples will also be assayed for QA, amino acids and neuropeptides. The long-range aim of the project is to define the neurochemical pathways in HD in sufficient detail to guide pharmacological intervention.