Patients throughout the world with type 1 Gaucher's disease are benefiting from enzyme replacement therapy that was developed by DMNB. The required enzyme, glucocerebrosidase, was originally isolated from human placental tissue. It is now being produced recombinantly in chinese hamster ovary cells. The recombinant enzyme has been approved by the FDA. Patients with Gaucher's disease on enzyme replacement therapy are gradually being phased from the placental preparation enzyme to recombinantly produced enzyme. We are currently exploring enzyme replacement therapy for patients with chronic neuronpathic (Type 3) Gaucher's disease. All of the patients that were treated had increases in hemoglobin, blood platelets, reduction of hepatosplenomegaly and improvement of their skeletal problems. However, the response of central nervous system involvement in these patients to enzyme replacement therapy varied. Some patients appeared to be stabilized with regard to the myoclonic seizures that is a hallmark of this phenotype. In a few, the onset of seizures was either delayed or perhaps even prevented. In two patients, however, there was evidence of progression of CNS involvement. We shall continue to evaluate enzyme replacement therapy in additional patients with Type 3 Gaucher's disease to attempt to determine their response to this treatment, and in particular, whether the CNS involvement can be prevented or reversed. Patients with Gaucher's disease rarely develop antibodies to exogenous glucocerebrosidase. When they occur, they are usually transient and do not interfere with the efficacy of the enzyme. One of our type 3 Gaucher patients developed a neutralizing (blocking) antibody to macrophage-targeted human placental glucocerebrosidase (Ceredase). Clinical signs associated with Gaucher's disease (reduction of hemoglobin, platelets, increased liver and spleen size and bony infarctions) recurred. We developed a successful procedure to reduce the titer of the neutralizing antibody in this patient and he subsequently responded satisfactorily to enzyme replacement.
