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The Children’s Memorial Health Institute, Warsaw, Poland.
Am J Med Genet A 2011;155A:2257–62.
Editor’s note: Mucopolysaccharidosis type II (MPS II, or Hunter syndrome) is an X-linked disease characterized by impaired activity of the lysosomal enzyme iduronate-2-sulfatase (IDS), which is involved in the degradation of the glycosaminoglycans (GAGs) dermatan sulfate (DS) and heparan sulfate (HS). As a result of the impaired degradation of these GAGs, DS and HS accumulate in various tissues and organs, thereby contributing to the signs and symptoms of the disease. Enzyme replacement therapy (ERT) with idursulfase is effective in ameliorating some symptoms; however, intravenously administered recombinant enzyme cannot cross the blood–brain barrier. Furthermore, in some reports, a low rate of penetration of the recombinant enzyme into the bones and joints is indicated. Gene expression-targeted isoflavone therapy (GET IT) is an experimental treatment based on the isoflavone genistein, which indirectly impairs the efficiency of GAG synthesis via the inhibition of epidermal growth factor receptor phosphorylation. The results of in vitro studies indicate that genistein slows the synthesis of some GAGs, particularly DS and HS. Slow GAG synthesis could prevent their further accumulation in cells, potentially enabling any residual activity of IDS to reduce the level of GAGs that have already accumulated and the achievement of a new balance between GAG synthesis and degradation.