PROSPECTIVE-STUDY OF NEUROLOGICAL RESPONSES TO TREATMENT WITH MACROPHAGE-TARGETED GLUCOCEREBROSIDASE IN PATIENTS WITH TYPE-3 GAUCHERS-DISEASE

We prospectively evaluated the clinical and biochemical responses to e nzyme-replacement therapy (ERT) with macrophage-targeted glucocerebros idase (Ceredase) infusions in 5 patients (age, 3.5-8.5 years) with typ e 3 Gaucher's disease. The patients were followed for up to 5 years. E nzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemi c manifestations of the disease regressed in all patients. Neurologica l deficits remained stable in 3 patients and slightly improved in 1. O ne patient developed myoclonic encephalopathy. Cognitive deterioration occurred in 1 patient and electroencephalographic deterioration in 2. Sequential cerebrospinal fluid (CSF) samples were obtained during the first 3 years of treatment in 3 patients and were analyzed for bioche mical markers of disease burden. Glucocerebroside and psychosine level s were not elevated in these specimens, whereas chitotriosidase and qu inolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treat ment implies a decreased number of Gaucher sells in the cerebral periv ascular space. Similar changes were not observed in the patient who ha d a poor neurological outcome. In conclusion, ERT reverses systemic ma nifestations of type 3 Gaucher's disease and appears to reduce the bur den of Gaucher cells in the brain-CSF compartment in some patients.