Gaucher disease: Progress and ongoing challenges

Mol Genet Metab. 2017 Jan-Feb;120(1-2):8-21. doi: 10.1016/j.ymgme.2016.11.006. Epub 2016 Nov 17.


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.

Keywords: Dr. Roscoe Brady; Enzyme replacement therapy; Gaucher disease; Glucocerebrosidase; Lysosomal storage disorder; Parkinsonism.

Publication types

  • Biography
  • Historical Article
  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Enzyme Replacement Therapy
  • Gaucher Disease / genetics
  • Gaucher Disease / therapy*
  • Genetic Therapy
  • Glucosylceramidase / genetics*
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Mice
  • Mutation*
  • National Institutes of Health (U.S.)
  • Small Molecule Libraries / therapeutic use
  • United States


  • Small Molecule Libraries
  • Glucosylceramidase

Personal name as subject

  • Roscoe Owen Brady