Journal of Inherited Metabolic Disease

, Volume 33, Issue 1, pp 61–67 | Cite as

Storage correction in cells of patients suffering from mucopolysaccharidoses types IIIA and VII after treatment with genistein and other isoflavones

  • Audrey Arfi
  • Magali Richard
  • Christelle Gandolphe
  • Daniel Scherman
Original Article


Mucopolysaccharidoses are autosomal and recessive lysosomal storage disorders caused by the deficiency of a lysosomal enzyme involved in glycosaminoglycan catabolism. The Sanfilippo type A disease (MPS III A) results from sulfamidase deficiency, which leads to accumulation of heparan sulfate, whereas Sly disease (MPS VII) results from beta-glucuronidase deficiency, leading to accumulation of heparan, dermatan, and chondroitin sulfates. These syndromes are characterized by severe central nervous system degeneration, resulting in progressive mental retardation, and fatality occurs in severely affected children. To date, no effective treatment is available except for bone marrow transplantation in specific cases. Recently, the use of genistein, an isoflavone that inhibits glycosaminoglycans synthesis, has been tested as substrate reduction therapy for neuronopathic forms of these diseases. We tested five natural analogs to genistein in human fibroblasts from both Sanfilippo A and Sly patients. Four molecules were as efficient as genistein in decreasing glycosaminoglycan accumulation. Moreover, a combination of several isoflavones was more efficient than one single isoflavone, suggesting a synergistic effect. These preliminary data may offer new perspectives for treating Sly and Sanfilippo A diseases and could be relevant to other neurological forms of mucopolysaccharidoses.


Genistein Isoflavones Daidzein Formononetin Glycitein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.







Lysosomal storage disease


Central nervous system


Enzyme replacement therapy


Substrate deprivation therapy


Substrate reduction therapy


Dimethylmethylene blue



We thank C. Caillaud for providing human fibroblasts derived from healthy volunteers. We also thank very much G. Chabot for all his advices regarding the isoflavone selection. This work was supported by the 6th PCRDT European “CLINIGENE” Network of Excellence and the MOLEDA STREP. A.A. received sponsorship from CLINIGENE.


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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Audrey Arfi
    • 1
    • 2
    • 3
    • 4
    • 5
  • Magali Richard
    • 1
    • 2
    • 3
    • 4
    • 5
  • Christelle Gandolphe
    • 1
    • 2
    • 3
    • 4
    • 5
  • Daniel Scherman
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Inserm, U640ParisFrance
  2. 2.CNRS, UMR8151ParisFrance
  3. 3.Faculté de Pharmacie, Chemical and Genetic Pharmacology LaboratoryUniversité Paris DescartesParisFrance
  4. 4.Ecole Nationale Supérieure de Chimie de ParisParisFrance
  5. 5.CNRS UMR 8151, Inserm, U640, Faculté de PharmacieParisFrance

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