title: Gaucher disease: Progress and ongoing challenges.
abstract: Over the past decades, tremendous progress has been made in the field of Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Many of the colossal achievements took place during the course of the sixty-year tenure of Dr. Roscoe Brady at the National Institutes of Health. These include the recognition of the enzymatic defect involved, the isolation and characterization of the protein, the localization and characterization of the gene and its nearby pseudogene, as well as the identification of the first mutant alleles in patients. The first treatment for Gaucher disease, enzyme replacement therapy, was conceived of, developed and tested at the Clinical Center of the National Institutes of Health. Advances including recombinant production of the enzyme, the development of mouse models, pioneering gene therapy experiments, high throughput screens of small molecules and the generation of induced pluripotent stem cell models have all helped to catapult research in Gaucher disease into the twenty-first century. The appreciation that mutations in the glucocerebrosidase gene are an important risk factor for parkinsonism further expands the impact of this work. However, major challenges still remain, some of which are described here, that will provide opportunities, excitement and discovery for the next generations of Gaucher investigators.
authors.affiliation: Yale University School of Medicine, Department of Internal Medicine, 333 Cedar Street, LMP 1080, P.O. Box 208019, New Haven, CT 06520-8019, United States. Electronic address: Pramod.mistry@yale.edu.
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mistry
authors.affiliation: Medical Genetics Branch, NHGRI, NIH, Bldg 35A Room 1E623, 35 Convent Drive, Bethesda, MD 20892, United States. Electronic address: glopez@mail.nih.gov.
authors.forename: Grisel
authors.initials: G
authors.lastname: Lopez
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX 75226, United States. Electronic address: Raphael.Schiffmann@BSWHealth.org.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Therapeutic Area Head Neuroscience, Shire plc, 300 Shire Way, Lexington, MA 02421, United States. Electronic address: nbarton@shire.com.
authors.forename: Norman W
authors.initials: NW
authors.lastname: Barton
authors.affiliation: University of Miami Miller School of Medicine, Department of Human Genetics and Medicine (Hematology), UHealth Sylvester Coral Springs, 8170 Royal Palm Boulevard, Coral Springs, FL 33065, United States. Electronic address: boneal@winning.com.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Weinreb
authors.affiliation: Medical Genetics Branch, NHGRI, NIH, Bldg 35A Room 1E623, 35 Convent Drive, Bethesda, MD 20892, United States. Electronic address: sidranse@mail.nih.gov.
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
mesh_terms: D000818:Animals; D056947:Enzyme Replacement Therapy; D005776:Gaucher Disease / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy; D005962:Glucosylceramidase / Q000235:genetics*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D051379:Mice; D009154:Mutation; D009316:National Institutes of Health (U.S.); D054852:Small Molecule Libraries / Q000627:therapeutic use; D014481:United States
chemical_list: D054852:Small Molecule Libraries; D005962:Glucosylceramidase
keywords: Dr. Roscoe Brady; Enzyme replacement therapy; Gaucher disease; Glucocerebrosidase; Lysosomal storage disorder; Parkinsonism