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 enzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease.


METHODS
Patients with type 3 Gaucher's disease (n = 21), aged 8 months to 35 years, were enrolled in a prospective study. Enzyme dose was adjusted to control systemic manifestations. Clinical and laboratory evaluations were 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 markedly decreased, and bone structure improved. Nineteen patients had asymptomatic interstitial lung disease unresponsive to ERT. Supranuclear gaze palsy remained stable in 19 patients, worsened in one patient, and improved in one. Cognitive function remained unchanged or improved over time 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.
Altarescu
G
G
Developmental and Metabolic Neurology Branch, Biometry and Fields Studies Branch, National Institute of Neurological Disorders and Stroke, W. G. Magnuson Clinical Center, National Institutes of Health, Bethesda 20892-1260, Maryland, USA.
Hill
S
S
Wiggs
E
E
Jeffries
N
N
Kreps
C
C
Parker
C C
CC
Brady
R O
RO
Barton
N W
NW
Schiffmann
R
R
D000293:Adolescent; D000328:Adult; D000365:Age Determination by Skeleton; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography / Q000379:methods; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D005962:Glucosylceramidase