Replacement Therapy for Inherited Enzyme Deficiency — Macrophage-Targeted Glucocerebrosidase for Gaucher's Disease

Barton, Norman W.; Brady, Roscoe O.; Dambrosia, James M.; Bisceglie, Adrian M. Di; Doppelt, Samuel H.; Hill, Suvimol; Mankin, Henry J.; Murray, Gary J.; Parker, Robert I.; Argoff, Charles E.; Grewal, Raji P.; Yu, Kian-Ti

doi:10.1056/nejm199105233242104

Cited by 1,167 publications

(610 citation statements)

References 17 publications

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“…However, in other lipid storage disorders such as Gaucher's disease low amounts of substituted enzyme are sufficient to reverse glucocerebroside storage, and upon BMT in mice with Sandhoff's disease the amount of gangliosides in the liver was substantially reduced although only 40% of normal ␤-hexosaminidase activity was reached in this organ. 19,20 Thus, compared with other lipid storage diseases stored sulfatide or ASA may have particular properties requiring comparatively large amounts of enzyme for amelioration of storage. The lysosomal deposition of sulfatide is paralleled by an enrichment of this sphingolipid in the cytoplasmic membrane and such membranes display physicochemical characteristics distinct from normal membranes.…”

Section: Figure 4 Cross-sectional Areas Of Axons Of Myelinated Fibersmentioning

confidence: 99%

Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations

et al. 2002

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Section: Figure 4 Cross-sectional Areas Of Axons Of Myelinated Fibersmentioning

confidence: 99%

Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations

et al. 2002

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“…For patients with type 1 (nonneuronopathic) GD, enzyme replacement therapy (ERT) has been the standard of care for more than 20 years 3.…”

Section: Introductionmentioning

confidence: 99%

Enzyme replacement therapy with taliglucerase alfa: 36‐month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase

Pastores

Shankar

Petakov³

et al. 2016

American J Hematol

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Taliglucerase alfa is the first available plant cell‐expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB‐06‐002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB‐06‐002 who continued receiving taliglucerase alfa in extension Study PB‐06‐003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB‐06‐003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30–33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, −1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), −19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, −51.5% (±8.1%; n = 10); and CCL18 concentration, −36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment‐related adverse events were mild or moderate and transient. The 36‐month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661–665, 2016. © 2016 Wiley Periodicals, Inc.

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“…[2] This disorder is characterized by an enlarged liver and spleen, anemia, painful bone lesions and in some cases neurological damage. The standard treatment for individuals with GCase deficiencies involves either enzyme replacement therapy with imiglucerase (Cerezyme, Genzyme Corp.) [3] or less frequently, substrate reduction therapy with mi-glustat (Zavesca, Actelion Ltd.). [4,5] Recently a third therapeutic approach, enzyme enhancement therapy (EET), utilizing small molecule pharmacological chaperone (PC) has been proposed.…”

mentioning

confidence: 99%

Isofagomine Induced Stabilization of Glucocerebrosidase

Kornhaber¹,

Tropak

Maegawa

et al. 2008

ChemBioChem

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Structurally destabilizing mutations in acid β-glucosidase (GCase) can result in Gaucher disease (GD). The iminosugar isofagomine (IFG), a competitive inhibitor and a potential pharmacological chaperone of GCase, is currently undergoing clinical evaluation for the treatment of GD. An X-ray crystallographic study of the GCase-IFG complex revealed a hydrogen bonding network between IFG and certain active site residues. It was suggested that this network may translate into greater global stability. Here it is demonstrated that IFG does increase the global stability of wild-type GCase, shifting its melting curve by ~15 °C and that it enhances mutant GCase activity in pretreated N370S/N370S and F213I/L444P patient fibroblasts. Additionally, amide hydrogen/ deuterium exchange mass spectroscopy (H/D-Ex) was employed to identify regions within GCase that undergo stabilization upon IFG-binding. H/D-Ex data indicate that the binding of IFG not only restricts the local protein dynamics of the active site, but also propagates this effect into surrounding regions.

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Replacement Therapy for Inherited Enzyme Deficiency — Macrophage-Targeted Glucocerebrosidase for Gaucher's Disease

Abstract: Intravenous administration of macrophage-targeted glucocerebrosidase produces objective clinical improvement in patients with type 1 Gaucher's disease. The hematologic and visceral responses to enzyme replacement develop more rapidly than the skeletal response.

Cited by 1,167 publications

References 17 publications

Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations

Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations

Enzyme replacement therapy with taliglucerase alfa: 36‐month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase

Isofagomine Induced Stabilization of Glucocerebrosidase

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