MANAGEMENT OF NEUTRALIZING ANTIBODY TO CEREDASE IN A PATIENT WITH TYPE-3 GAUCHER-DISEASE

Objectives. The beneficial effects of macrophage-targeted glucocerebro sidase (Ceredase) in patients with Gaucher disease are well establishe d. A minority of recipients develop transient nonneutralizing antibodi es to the exogenous enzyme. A 7-year-old patient with type 3 Gaucher d isease whose clinical course began to deteriorate while receiving Cere dase developed a progressively increasing titer of IgG antibody that b locked the catalytic activity of Ceredase. We sought to develop a stra tegy that would restore the benefit of enzyme replacement therapy in t his patient. Methods. The patient was treated with two courses of a co mbination of plasma exchange, cydophosphamide, intravenous IgG, and la rge doses of Ceredase. Results. After the second course of this regime n, the titer of the neutralizing antibody in the blood gradually decli ned to negligible levels. Clinical parameters that had been deteriorat ing (reduction of hemoglobin level, increased serum acid phosphates ac tivity, repeated skeletal infarctions, progressive enlargement and inf arction of the spleen) all improved. There has been no recurrence of t he neutralizing antibody in this patient. Conclusions. Very few patien ts with Gaucher disease who are treated with Ceredase develop a neutra lizing antibody to the exogenous enzyme. In the rare instances where t his phenomenon occurs, it is likely that the strategy we have used (pl asma exchange, cyclophosphamide, intravenous IgG, and large doses of e nzyme) may provide benefit to such individuals. It is also likely that this technique may be helpful when enzyme replacement therapy is atte mpted in patients with other disorders in which the genetic mutation a brogates the production of the protein (CRIM-negative individuals).