Lysosomal Storage Disorders (eBook)

John A. Barranger, M.D., Ph.D., is a tenured professor in the departments of human genetics, molecular genetics and biochemistry, and pediatrics at the University of Pittsburgh. He is also director of the Human Gene Therapy Applications Laboratory, the Center for the Study and Treatment of Jewish Genetic Diseases, and the Comprehensive Gaucher Disease Treatment Center. Additionally, he is co-director of the Human Gene Therapy Center. Previously, Dr. Barranger was a clinical associate at the National Institutes of Health (NIH), where, from 1976 to 1978, he served in the clinical investigations and therapeutics section, Developmental and Metabolic Neurology Branch (DMNB), National Institute of Neurological and Communicative Disorders and Stroke. He ultimately became chief of the molecular and medical genetics section of the DMNB and associate branch chief. Dr. Barranger received a doctorate and medical degree from the University of Southern California Los Angeles, and completed an internship and residency in pediatrics at the University of Minnesota. Dr. Barranger has devoted his professional career to the study of inherited metabolic diseases, particularly lysosomal storage disorders. His research interests include biochemical and molecular genetics, enzyme therapy, gene transfer, and models of genetic disease. As a result of his investigation of the structure of glucocerebrosidase and receptors on macrophages, Dr. Barranger developed successful enzyme replacement therapy for Gaucher disease, an inherited, potentially lethal lysosomal disorder that affects more than 10,000 people in the United States. This therapy received Food and Drug Administration approval in 1991 and serves as a treatment model for more than 50 related lysosomal storage disorders. Currently, Dr. Barranger is focused on developing models of inherited diseases to study their pathobiology and treatment by enzyme and gene therapy.Included among Dr Barranger's honors are the March of Dimes Health Career Award, United States Public Health Service Commendation Medal, Arthur S. Flemming Award and the Scientific Achievement Award of the National Gaucher Foundation. In addition to consulting for government and industry, Dr Barranger is a member of numerous professional organizations, including the American Society of Biochemistry and Molecular Biology, American Society of Human Genetics, Society for Inherited Metabolic Disorders, and the Society for Pediatric Research.   Mario A. Cabrera-Salazar, MD is a Staff Scientist at Genzyme Corporation in Framingham. MA. He is involved in the development of enzymatic and gene therapies for lysosomal storage disorders and for neurodegenerative diseases in the department of Genetic Disease Science.

Preface 6
Contents 7
Contributors 10
FROM LYSOSOMES TO STORAGE DISEASES AND BACK: A PERSONAL REMINISCENCE 17
LYSOSOMAL BIOGENESIS AND DISEASE 22
THE CONCEPT OF TREATMENT IN LYSOSOMAL STORAGE DISEASES 52
COMPLEX LIPID CATABOLISM 59
RETROVIRAL VECTORS FOR GENE THERAPY 67
ADENOVIRUS IN GENE THERAPY 82
SETTING BACK THE CLOCK: ADENOVIRAL-MEDIATED GENE THERAPY FOR LYSOSOMAL STORAGE DISORDERS 94
ADENO-ASSOCIATED VIRAL-MEDIATED GENE THERAPY OF LYSOSOMAL STORAGE DISORDERS 109
HERPES SIMPLEX VIRUS VECTORS FOR GENE THERAPY OF LYSOSOMAL STORAGE DISORDERS 122
GENE THERAPY OF LYSOSOMAL STORAGE DISORDERS BY LENTIVIRAL VECTORS 143
SUBSTRATE REDUCTION THERAPY 162
NEWBORN SCREENING FOR LYSOSOMAL STORAGE DISORDERS 178
GENETIC COUNSELING FOR LYSOSOMAL STORAGE DISEASES 188
NEURAL STEM CELL THERAPY IN LYSOSOMAL STORAGE DISORDERS 205
THE GM1 GANGLIOSIDOSES 225
THE GM2 GANGLIOSIDOSES 237
ACID SPHINGOMYELINASE-DEFICIENT NIEMANN– PICK DISEASE 265
KRABBE DISEASE (GLOBOID CELL LEUKODYSTROPHY) 277
METACHROMATIC LEUKODYSTROPHY 292
FABRY DISEASE 314
GAUCHER DISEASE: REVIEW AND PERSPECTIVES ON TREATMENT 326
OF GAUCHER DISEASE THERAPEUTIC GOALS IN THE TREATM ENT 351
THE NEURONAL CEROID LIPOFUSCINOSES: CLINICAL FEATURES AND MOLECULAR BASIS OF DISEASE 377
MUCOPOLYSACCHARIDOSIS I 395
MUCOPOLYSACCHARIDOSIS II 412
SANFILIPPO SYNDROME: CLINICAL GENETIC DIAGNOSIS AND THERAPIES 420
MUCOPOLYSACCHARIDOSIS IV ( Morquio Syndrome MPS IV)
MUCOPOLYSACCHARIDOSIS TYPE VI ( MPS VI, Maroteaux– Lamy Syndrome) 451
MUCOPOLYSACCHARIDOSIS TYPE VII (SLY DISEASE): CLINICAL, GENETIC DIAGNOSIS AND THERAPIES 461
POMPE DISEASE-GLYCOGENOSIS TYPE II: ACID MALTASE DEFICIENCY 477
LYSOSOMAL FREE SIALIC ACID STORAGE DISORDERS: SALLA DISEASE AND ISSD 503
CYSTINOSIS 516
I-CELL DISEASE 531