title: Niemann-Pick disease, type C and Roscoe Brady.
abstract: The Niemann-Pick family of diseases was poorly understood until Roscoe Brady and his colleagues began their investigations in the 1960s. Following Brady's discovery of the defect in acid sphingomyelinase in Niemann-Pick disease, types A and B, Peter Pentchev, a senior scientist in the group, launched a series of investigations of an unusual lipid storage disease in a spontaneous mouse model. These led initially to identification of the cholesterol trafficking defect in the mouse, and then in human Niemann-Pick disease, type C (NPC). This discovery formed the basis of the standard diagnostic test for NPC for the next three decades. Subsequently, an international collaboration was established, based at the Brady lab at NIH, which culminated in discovery of the NPC1 gene. Roscoe Brady, Peter Pentchev and their colleagues defined and refined the clinical biochemical and pathological phenotypes of NPC in a series of elegant parallel studies. They also identified abnormal oxysterols in NPC; later work has proved such compounds to be sensitive biomarkers of the disease. The dedication of the Brady lab to NPC, and the discoveries that flowed therefrom, provided critical foundations for the current explosion of progress in this disease.
authors.affiliation: Department of Neurology, Mayo Clinic Children's Center, RO_MA_16_03ECON, 200 First Street SW, Rochester, MN 55905, United States; Department of Pediatrics and Medical Genetics, Mayo Clinic Children's Center, RO_MA_16_03ECON, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: patterson.marc@mayo.edu.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Patterson
authors.affiliation: Department of Neuroscience, Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, New York, NY, United States. Electronic address: Steve.walkley@einstein.yu.edu.
authors.forename: Steven U
authors.initials: SU
authors.lastname: Walkley
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D009154:Mutation; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism*; D000072376:Oxysterols
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D000072376:Oxysterols; D002784:Cholesterol
keywords: Biomarkers; Cholesterol; Cyclodextrin; Filipin; Gangliosides; Miglustat; Niemann-Pick disease; Oxysterols; Roscoe Brady; Type C