Enzyme Replacement Therapy Carolyn Sinow Biochem 118 Professor Brutlag December 2 2010 Lysosomal Storage Diseases LSD Lysosome organelle responsible for catabolyzing macromolecules Characterized by deficiency of lysosomal enzyme Group of over 40 diseases Most are autosomal recessive Combined incidence of 1 6500 7500 live births Enzyme Replacement Therapy ERT Cultivate missing enzyme outside the human body and then administer it to patients as treatment Can be used for diseases besides LSD First suggested in 1960s by Roscoe Brady Treats the cause not just the symptoms Creation of ERT Plasmid Chinese Hamster Ovary Cells Animal models Purification Clinical Trials Currently ERT for 6 Lysosomal storage diseases Gaucher s Disease 1st developed ERT Most common of the lysosomal storage diseases Deficient enzyme Glucocerebrodase catabolyzes glucoceramide Affects spleen liver bone marrow 3 clinical subtypes Gaucher Disease type 1 lethal by 2 years old Cerezyme ERT reverses pathologies near normal lives http geneticpeople com p 276 Fabry Disease X linked inheritance Deficient enzyme galactosidase catabolyzes globotriaosylceramide Symptoms Usually begin in adolescence Acroparesthesias Pain and gastrointestinal problems Fabrazyme Prevents but does not reverse damage Pain remains Pompe Disease A k a Glycogen storage disease type II Deficient enzyme http www fightpompe com article glucosidase 45 fight pompe around the world Onset infant adulthood Skeletal muscle problems Myozyme ERT prolongs infant life increases motor abilities Clinical trials still in process for late onset Pompe http www joemcdowellphotography com Haley Haley 1903403 Mpc3n 3 97982714 W 9w3V 97982714 W9w3V Mucopolysaccharidoses MPS Group of 6 diseases Glycosaminoglycans accumulate 3 types have treatment MPS I Hurler or HurlerScheie syndrome L iduronidase MPS II Hunter syndrome X linked inheritance Iduronate sulfatase MPS VI Maroteaux Lamy syndrome Arylsulfatase Mucopolysaccharidoses Common symptoms coarse facies deafness cardiac disease delayed development neurologic problems I VI Hurler Hunter Maroteaux Lamy http www metabolica org start node 8 http chad pyper last memories com Bone marrow transplant Hurler Enzyme replacement therapies http www maroteauxlamy com English hcp AboutMPS a spx Aldurazyme Hurler 2003 Elaprase Hunter 2006 Naglazyme Maroteaux Lamy 2005 Non lysosomal storage diseases Can correct symptoms not disease Cystic fibrosis has problems with pancreatic ducts that prevents enzymes from reaching gastrointestinal tract Pancreatitis Pancreatic and periampullary cancer Shortcomings of ERT Admistered Infusions Side via IV once every 2 weeks last 2 6 hours Effects Allergy symptoms respiratory distress Long term effects not yet known Gaucher s treated for 15 20 years with no severe side effects Antibody responses IgG binds to drugs allergy symptoms IgE increased risk of anaphylactic reaction Cost 200 000 300 000 per year Can Affects max out health insurance in 2 5 years employment Sources Laurie Bailey An Overview of Enzyme Replacement Therapy for Lysosomal Storage Diseases The Online Journal of Issues in Nursing 2006 Web Stirnemann Jerome Anne Boutten Corine Vincent and Arsene Mekinian Impact of Imiglucerase on the Serum Glycosylated ferritin Level in Gaucher Disease Blood Cells Molecules and Diseases 2010 Print What Is Enzyme Replacement Therapy WiseGEEK Clear Answers for Common Questions Web 02 Dec 2010 http www wisegeek com what is enzyme replacementtherapy htm Imrie CW G Connett RI Hall and RM Charnley Review Article Enzyme Supplementation in Cystic Fibrosis Chronic Pancreatitis Pancreatic and Periampullary Cancer Aliment Pharmacol Ther 1st ser 32 2010 1 25 Print
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