The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease

Objective: To assess the long-term systemic and neurologic responses to enz yme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase i n patients with type 3 Gaucher's disease. Study design: Patients with type 3 Gaucher's disease (n = 21), aged 8 month s to 35 years, were enrolled in a prospective study. Enzyme dose was adjust ed to control systemic manifestations. Clinical and laboratory evaluations were performed at baseline and every 6 to 12 months thereafter. Patients we re followed up for 2 to 8 years. Results: Significant improvement in hemoglobin levels, platelet count, and acid phosphatase values occurred. Liver and spleen volume markedly decrease d, and bone structure improved. Nineteen patients bad asymptomatic intersti tial lung disease unresponsive to ERT. Supranuclear gaze palsy remained sta ble in 19 patients, worsened in one patient, and improved in one. Cognitive function remained unchanged or improved over time in 13 patients but decre ased in 8 patients, 3 of whom developed progressive myoclonic encephalopath y accompanied by cranial magnetic resonance imaging and electroencephalogra phic deterioration. Conclusions: At relatively high doses, ERT reverses almost all the systemic manifestations in patients with type 3 Gaucher's disease. Most treated pat ients do not deteriorate neurologically, Novel therapeutic strategies are r equired to reverse the pulmonary and neuronopathic aspects of the disease.