Following the remarkable success of enzyme replacement therapy in patients with type 1 (non-neuronopathic) Gaucher disease, we have examined the effect of this treatment in patients with type 3 (chronic neuronopathic) Gaucher disease. Marked improvement of the systemic manifestations of the disorder occurred in this cohort, but the neurological response varied. Neurological signs in patients with horizontal gaze paresis remained stable, or in some cases, appeared to improve. Patients with myoclonus epilepsy did not respond to intravenously administered enzyme. In order to increase the chance for successful therapy in the latter patients and in those with type 2 (acute neuronopathic) Gaucher disease, we, in collaboration with the Surgical Neurology Branch, NINDS, developed a procedure for the direct intracerebral administration of the requisite glucocerebrosidase. We plan to examine the safety of this therapeutic approach in patients with type 2 Gaucher disease in the coming year. If successful, the efficacy of this technique will be determined. If it is beneficial, we will explore this procedure in patients with other lysosomal storage disorders such as Tay-Sachs disease that are characterized by extensive cerebral involvement. We have completed a phase 1 safety and dose- escalation trial of enzyme replacement therapy in patients with Fabry disease. Because of significant reductions of accumulated ceramidetrihexoside in the liver and in urinary sediment of the recipients, we embarked on, and have nearly completed, a phase 2 double blind, placebo-controlled clinical efficacy trial of enzyme replacement therapy in patients with Fabry disease. - Gaucher, Fabry, Niemann-Pick Diseases, Enzyme Replacement Therapy - Human Subjects
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