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Enzyme Therapy in Gaucher Disease Type 1: Effect of Neutralizing Antibodies to Acid  -Glucosidase
Elvira Ponce,
Jay Moskovitz, and
Gregory Grabowski
From the Division of Human Genetics, Children's Hospital Research Foundation, Cincinnati, OH.
Gaucher disease type 1, a non-neuronopathic lysosomal storage disease, is caused by mutations at the acid  -glucosidase locus. Periodic infusions of macrophage-targeted acid -glucosidase reverse hepatosplenomegaly, hematologic, and bony findings in many patients. Two patients receiving enzyme therapy developed neutralizing antibodies to acid -glucosidase that were associated with a lack of improvement or progressive disease. After initial improvement, case 1 had no additional response to 2 years of high-dose (50 U/kg every 2 weeks) enzyme therapy. Similarly, case 2 initially showed a favorable response to enzyme therapy that plateaued after 1 year of treatment. Both patients developed minor allergic reactions and antibodies to acid -glucosidase within the first 6 months of treatment. Enzyme therapy was discontinued in case 1, with resultant disease progression and need for splenectomy. An immunosuppression/tolerization protocol was initiated in case 2 because of disease progression and stable neutralizing antibody titers. The IgG neutralizing antibodies rapidly and completely inactivated the wild-type, but not the N370S, acid -glucosidase in vitro. Antibodies to human serum albumin and chorionic gonadotropin also developed. The finding of neutralizing antibodies to acid -glucosidase during enzyme therapy for Gaucher disease has significant implications for monitoring the therapeutic responses and for potential alternative future therapies for Gaucher disease.
Blood, Vol. 90 No. 1 (July 1), 1997:
pp. 43-48
© 1997 by The American Society of Hematology.
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