Gaucher disease, enzyme

Figure 11 Enzymatic activity profile of man rose-terminal ghicocerebraidase in plasma of a boy with Gaucher disease. Enzyme was infused over 4 hours at a constant rate of 1225 Uftg. A steady-stale value of 10.6 mUftnL was achieved during the first hour. When the infusion was terminated at 240 minutes, enzyme was cleared from the plasma by a firat-order process with an elimination half-life of 6.3 minutes. The dashed line represent the activity profile calculated from the observed kinetic constants.

Lysosomotropic after intravenous injection to treat enzyme deficiencies (e.g., adult Gaucher s disease) Enzymes... 

K. M. Osiecki-Newman, D. Fabbro, T. Dinur, S. Boas, S. Gatt, G. Legler, R. J. Desnick, and G. A. Grabowski, Human acid p-glucosidase Affinity purification of the normal placental and Gaucher disease splenic enzymes on N-alkyl-deoxynojirimycin-sepharose, Enzyme, 35 (1986) 147-153. 

One example is an enzyme replacement drug used to treat a form of Gaucher disease, which is caused by an inherited error in the gene coding for the enzyme that breaks down the fatty substance cerebroside. In Gaucher disease, certain immune system cells... 

Like many recombinant treatments for chronic diseases, the recombinant replacement enzyme for Gaucher disease is very expensive A year s treatment can cost over 150,000, though most private insurance companies will reimburse patients for its use. 

Grabowski, G.A., N.W. Barton, G. Pastores, J.M. Dambrosia, T.K. Banerjee, M.A. McKee, C. Parker, R. Schiffmann, S.C. HiU, and R.O. Brady, Enzyme therapy in type 1 Gaucher disease comparative efficacy of mannose-terminated glucocerebrosidase... 

Brady, R.O., and N.W. Barton, Enzyme replacement therapy for Gaucher disease critical investigations beyond demonstration of clinical efficacy. Biochem Med Metab Biol, 1994.52(1) 1-9. 

Long-term enzyme replacement therapy for patients with a confirmed diagnosis of type 1 Gaucher disease... 

This enzyme is increased in Gaucher disease and may also be increased, but to a lesser extent, in other sphingolipidoses such as Niemann-Pick disease type A/ and NPC, Krabbe disease, and GM1-gangliosidosis. The assay is based on the method described by Hollak et al. [22] and Guo et al. [17]. 

The most commonly used therapy to treat LSDs is heterologous bone marrow transplantation (BMT). This treatment provides both normal bone marrow and bone marrow-derived cells, which release enzyme continuously. Unfortunately, BMT is associated with several problems and risks including the availability of a suitable donor, poor response to therapy, and sustained immune suppression. BMT therapies for MPS I, MPS II, MPS III, metachromatic leukodystrophy, and non-neuronopathic forms of Gaucher disease have demonstrated promising results. In most successful cases, the pathology is reversed in the visceral organs with variable or unclear success in the CNS (Laine et al., 2004). 

The clinical effects of mannose tenninai giuoocerebrosidase were initially examined in eight patients with non-neuionopathic, type 1 Gaucher disease. Seven of the patients were either adolescents or adults, and one was a 4-year-okl hoy, A total dose of 190 U of enzyme was administered intravenously to each of these patients weekly over a 6-month period. A beneficial effect was clearly evident only in (he youngest of the recipients [261 A dramatic increase in... 

RQund 10 Comparison Of skeletal involvement in a pretreatment radiograph or the left humerus (A) with an cximinitkm obtained on week 310 dining high-dose enzyme supplementation (B). Radiographic signs of Gaucher disease are not apparent cm the latter him. (non Ref. 27.)... 

General principles of enzyme replacement therapy for type 1 Gaucher disease can be developed at this time from the data presented in the preceding sections. Because the disease and its response to treatment are heterogeneous, the management of each patient most be individualized. At the outset of treatment, enzyme dosage should be selected based on the overall burden of disease and the... 

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