The efficacy of enzyme replacement therapy in patients with chronic neuronopathic gaucher’s disease

To assess the long-term systemic and neurologic responses toenzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidasein patients with type 3 Gaucher-s disease.Study design: Patients with type 3 Gaucher-s disease (n = 21) aged 8months to 35 years were enrolled in a prospective study. Enzyme dose wasadjusted to control systemic manifestations. Clinical and laboratory evaluationswere performed at baseline and every 6 to 12 months thereafter.Patients were followed up for 2 to 8 years.Results: Significant improvement in hemoglobin levels platelet count, and acid phosphatase values occurred. Liver and spleen volume markedlydecreased and bone structure improved. Nineteen patients had asymptomaticinterstitial lung disease unresponsive to ERT. Supranuclear gazepalsy remained stable in 19 patients worsened in one patient and improvedin one. Cognitive function remained unchanged or improved over time in in 13 patients but decreased in 8 patients 3 of whom developed progressive myoclonic encephalopathy accompanied by cranial magnetic resonance imaging and electroencephalographic deterioration. Conclusions: At relatively high doses ERT reverses almost all the systemic manifestations in patients with type 3 Gaucher's disease. Most treated patients do not deteriorate neurologically. Novel therapeutic strategies are required to reverse the pulmonary and neuronopathic aspects of the disease.