Glycoconjugate Journal

, Volume 13, Issue 2, pp 153–157 | Cite as

Treatment of Gaucher disease with an enzyme inhibitor

  • Norman S. Radin


The hypothesis is offered predicting that Caucher patients could be treated with a drug that slows the synthesis of glucosylceramide, the lipid that accumulates in this disorder. The present therapeutic approach involves augmenting the defective enzyme, glucosylceramide β-glucosidase, with exogenous β-glucosidase isolated from human tissue. This spectacularly expensive mode of treatment should be replaceable with a suitable enzyme inhibitor that simply slows formation of the lipid and matches the rate of synthesis with the rate of the defective, slowly working β-glucosidase. Several drugs that possess this ability are available, the best known of which is 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a designer inhibitor that resembles the synthase's substrate and product. PDMP has been found to be effective in mice, rats, fish, and a wide variety of cultured cells. Its use, at suitable dosages, seems to be harmless, although long-term tests have not been made. The lack of suitable animal models of Gaucher disease has made it difficult to test the hypothesis adequately, but PDMP does rapidly lower the levels of glucosylceramide in normal animal tissues and the animals evidently do well with the lowered levels of glucosylceramide and its more complex glycolipid metabolites.


glucosylceramidase insufficiency Gaucher disease chemotherapy glucosylceramide synthease inhibition PDMP (1-phenyl-2-decanoylamino-3-morpholino-1-propanol) 









Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Inokuchi J, Radin NS (1987)J Lipid Res 28: 565–71.Google Scholar
  2. 2.
    Shukla A, Radin NS (1991)J Lipid Res 32: 713–22.Google Scholar
  3. 3.
    Shukla G, Shukla A, Inokuchi J, Radin NS (1991)Biochim Biophys Acta 1083: 101–8.Google Scholar
  4. 4.
    Sundaram KS, Lev M (1984)J Neurochem 42: 577–81.Google Scholar
  5. 5.
    Fenderson BA, Ostrander GK, Hausken Z, Radin NS, Hakomori S (1992)Exp Cell Res 198: 362–66.Google Scholar
  6. 6.
    Inokuchi J, Mason I, Radin NS (1987)Cancer Lett 38: 23–30.Google Scholar
  7. 7.
    Shukla A, Shukla GS, Radin NS (1992)Am J Physiol 262: F24–29.Google Scholar
  8. 8.
    Datta SC, Radin NS (1988)Lipids 23: 508–10.Google Scholar
  9. 9.
    Zador IZ, Deshmukh GD, Kunkel R, Johnson K, Radin NS, Shayman, JA (1993)J Clin Invest 91: 797–803.Google Scholar
  10. 10.
    Shiran A, Brenner B, Laor A, Tatarsky I (1993)Cancer 72: 219–24.Google Scholar
  11. 11.
    Inokuchi J, Momosaki K, Shimeno H, Nagamatsu A, Radin NS (1989)J Cell Physiol 141: 573–83.Google Scholar
  12. 12.
    Svensson M, Lindstedt R, Radin NS, Svanborg C (1994)Infect Immun 62: 4404–10.Google Scholar
  13. 13.
    Abe A, Radin NS, Shayman JA, Wotring LL, Zipkin RE, Sivakumar R, Ruggieri JM, Carson KG, Ganem B (1995)J Lipid Res 36: 611–21.Google Scholar
  14. 14.
    Radin NS, Shayman JA, Inokuchi J (1993) InAdvances in Lipid Research: Sphingolipids in Signaling, Part B (Bell RM, Hannun YA, Merrill AH, eds), Vol. 28, pp. 183–213. Orlando: Academic Press.Google Scholar
  15. 15.
    Radin NS, Shayman JA (1993) InNeuroProtocols: A Companion to Methods in Neurosciences (Fisher SK, Bleasdale JE, eds), Vol. 3, pp. 145–55. Orlando: Academic Press.Google Scholar
  16. 16.
    Hospattankar V, Vunnam RR, Radin NS (1982)Lipids 17: 538–43.Google Scholar
  17. 17.
    Daniels LB, Coyle PJ, Glew RH, Radin NS, Labow RS (1982)Arch Neurol 39: 550–56.Google Scholar
  18. 18.
    Platt FM, Neises GR, Karlsson GB, Dwek RA, Butters TD (1994)J Biol Chem 269: 27108–14.Google Scholar
  19. 19.
    Vanderjagt DJ, Fry DE, Glew RH (1994)Biochem J 300: 309–15.Google Scholar
  20. 20.
    Datta SC, Radin NS (1988)Biochem Biophys Res Commun 152: 155–60.Google Scholar
  21. 21.
    Datta SC, Snider RM, Radin NS (1986)Biochim Biophys Acta 877: 387–98.Google Scholar
  22. 22.
    Rosenwald AG, Pagano RE (1994)J Lipid Res 35: 1232–40.Google Scholar

Copyright information

© Chapman & Hall 1996

Authors and Affiliations

  • Norman S. Radin
    • 1
  1. 1.Mental Health Research Institute and Division of Nephrology MSRBIIUniversity of MichiganAnn ArborUSA

Personalised recommendations