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Prospective study of neurological responses to treatment with macrophage‐targeted glucocerebrosidase in patients with type 3 Gaucher's disease
Author(s) -
Schiffmann Raphael,
Heyes Melvyn P.,
Aerts J. M.,
Dambrosia James M.,
Patterson Marc C.,
DeGraba Thomas,
Parker Colette C.,
Zirzow Gregory C.,
Oliver Katherine,
Tedeschi Gioacchino,
Brady Roscoe O.,
Barton Norman W.
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410420412
Subject(s) - glucocerebrosidase , glucocerebroside , medicine , enzyme replacement therapy , cerebrospinal fluid , disease , gaucher's disease , gastroenterology , prospective cohort study , encephalopathy
We prospectively evaluated the clinical and biochemical responses to enzyme‐replacement therapy (ERT) with macrophage‐targeted glucocerebrosidase (Ceredase) infusions in 5 patients (age, 3.5–8.5 years) with type 3 Gaucher's disease. The patients were followed for up to 5 years. Enzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemic manifestations of the disease regressed in all patients. Neurological deficits remained stable in 3 patients and slightly improved in 1. One 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 biochemical markers of disease burden. Glucocerebroside and psychosine levels were not elevated in these specimens, whereas chitotriosidase and quinolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treatment implies a decreased number of Gaucher cells in the cerebral perivascular space. Similar changes were not observed in the patient who had a poor neurological outcome. In conclusion, ERT reverses systemic manifestations of type 3 Gaucher's disease and appears to reduce the burden of Gaucher cells in the brain–CSF compartment in some patients.