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METHODS AND COMPOSITIONS FOR INCREASING ALPHA-L-IDURONIDASE ACTIVITY IN THE CNS

  • US 20090053219A1
  • Filed: 07/25/2008
  • Published: 02/26/2009
  • Est. Priority Date: 07/27/2007
  • Status: Active Grant
First Claim
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1. A method for treating an α

  • -L-iduronidase deficiency in the central nervous system of a subject in need thereof, comprising systemically administering to the subject a therapeutically effective dose of a fusion antibody having α

    -L-iduronidase activity, wherein;

    (i) at least about 0.5% of the therapeutically effective dose is delivered to the brain;

    (ii) the fusion antibody;

    comprises;

    (a) a fusion protein containing the amino acid sequence of an immunoglobulin heavy chain and an α

    -L-iduronidase, and (b) an immunoglobulin light chain;

    (iii) the fusion antibody binds to an extracellular domain of the human insulin receptor; and

    catalyzes hydrolysis of unsulfated alpha-L-iduronosidic linkages in dermatan sulfate; and

    (iv) the amino acid sequence of the α

    -L-iduronidase is covalently linked to the carboxy terminus of the amino acid sequence of the immunoglobulin heavy chain.

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