This will lead to thepresymptomatic detection of affecteds and the early and reliable diagnosisof carriers, which is not available at the present time. Our majorhypothesis is that a primary defect in lipid peroxidation leads to thegeneration of secondarylipid oxidation products, the 4-hydroxyalkenals, which go on to form autofluorescent chromolipids or ceroid which ispathognomic for NCL. Our preliminary data supports this idea. Gaschromatographic analysis has revealed, in agonist-stimulated activationASA of blood cells from a well-documented canine model of NCL, thataffected, carrier and normal dogs were clearly distinguishable by their HNElevels. A major aim is to classify NCL patients on a biochemical basis inorder to set the stage for their study on a molecular level. To this endwe have established a Repository of 100 immortalized human lymphocytes andDNAs from NCL patients and their unaffected family members. These celllines have been used in our assays and have been provided to investigatorsthroughout the world. We propose to expand our collection such that eachtype of NCL is well represented. This is especially important since all ofthese patients are moribund and there is a need to have standardizedreference facilities for all investigators to examine. Further, thesestudies will indicate which types of hum NCL correspond to the dog model. In addition, a biochemical understanding of how ceroid, the characteristicmarker for NCL, is formed will have implications for understanding thenatural process of cell aging.
Alcohol Dehydrogenase, Biomarker, Cell Bank Registry, Clone Cell, Disease Classification, Dog, Early Diagnosis, Family Genetics, Fatty Acid Metabolism, Human Subject, Lipid Peroxide, Lymphocyte, Molecular Pathology, Neural Degeneration, Neuronal Ceroid Lipofuscinosis, Peroxidation, Unsaturated Fatty Acid
