Competing for the treasure in exceptions

Cox, Timothy M.

doi:10.1002/ajh.23399

Cited by 13 publications

(14 citation statements)

References 20 publications

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“…[ 2 ] Enzyme replacement therapy (ERT) is a treatment paradigm wherein deficient enzyme is replaced via infusion of active enzyme; it is the standard of care for patients with GD. [ 4 ] Successful treatment of GD requires targeting of the infused enzyme to lysosomes within macrophages. This occurs via uptake of appropriately glycosylated enzyme to permit efficient uptake by mannose receptors on the surface of macrophages [ 5 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease

et al. 2015

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Taliglucerase alfa is a beta-glucocerebrosidase enzyme replacement therapy approved in the United States, Israel, and other countries for treatment of Type 1 Gaucher disease in adults, and is the first approved plant cell—expressed recombinant protein. In this report, taliglucerase alfa pharmacokinetics were assessed in adult and pediatric patients with Gaucher disease from separate multicenter trials of 30 Units/kg and 60 Units/kg doses infused every 2 weeks. Serial blood samples were obtained from adult patients following single-dose administration on day 1 (n = 26) and multiple doses at week 38 (n = 29), and from pediatric patients following administration of multiple doses of taliglucerase alfa for 10–27 months (n = 10). In both adult and pediatric patients, maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to last measureable concentration (AUC0-t), and from time zero to infinity (AUC0-∞) were higher after 60 Units/kg dose than 30 Units/kg dose. No tendency for accumulation or change in taliglucerase alfa pharmacokinetic parameters over time from day 1 to week 38 was observed with repeated doses of 30 or 60 Units/kg in adults. After multiple doses, mean (range) dose-normalized pharmacokinetic parameters were similar for adult versus pediatric patients receiving 60 Units/kg: Cmax expressed in ng/mL/mg was 42.4 (14.5–95.4) in adults and 46.6 (34.4–68.4) in pediatric patients, AUC0 t expressed in ng•h/mL/mg was 63.4 (26.3–156) in adults and 63.9 (39.8–85.1) in pediatric patients, t1/2 expressed in minutes was 34.8 (11.3–104) in adults and 31.5 (18.0–42.9) in pediatric patients and total body clearance expressed in L/h was 19.9 (6.25–37.9) in adults and 17.0 (11.7–24.9) in pediatric patients. These pharmacokinetic data extend the findings of taliglucerase alfa in adult and pediatric patients.Trial RegistrationClinicalTrials.gov. NCT00376168 (in adults); NCT01411228 (in children)

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease

et al. 2015

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“…Patients exhibit hepatomegaly and splenomegaly in addition to the ultimately lethal brain pathology ( Gupta et al, 2011 ). Enzyme replacement therapy (ERT) has been highly successful in treating the visceral pathology associated to GD ( Cox, 2013 ) and other lysosomal storage disorders ( Ortolano et al, 2014 ). However, the presence of the BBB has severely restricted recombinant enzyme from crossing into the CNS and rendering ERT ineffective in preventing death from neurodegeneration ( Pastores et al, 1993 ; Wynn et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Perinatal systemic gene delivery using adeno-associated viral vectors

Karda

Buckley

Mattar

et al. 2014

Front. Mol. Neurosci.

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Neurodegenerative monogenic diseases often affect tissues and organs beyond the nervous system. An effective treatment would require a systemic approach. The intravenous administration of novel therapies is ideal but is hampered by the inability of such drugs to cross the blood–brain barrier (BBB) and precludes efficacy in the central nervous system. A number of these early lethal intractable diseases also present devastating irreversible pathology at birth or soon after. Therefore, any therapy would ideally be administered during the perinatal period to prevent, stop, or ameliorate disease progression. The concept of perinatal gene therapy has moved a step further toward being a feasible approach to treating such disorders. This has primarily been driven by the recent discoveries that particular serotypes of adeno-associated virus (AAV) gene delivery vectors have the ability to cross the BBB following intravenous administration. Furthermore, safety has been demonstrated after perinatal administration mice and non-human primates. This review focuses on the progress made in using AAV to achieve systemic transduction and what this means for developing perinatal gene therapy for early lethal neurodegenerative diseases.

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“…[2] Enzyme replacement therapy (ERT) is a treatment paradigm wherein deficient enzyme is replaced via infusion of active enzyme; it is the standard of care for patients with GD. [4] Successful treatment of GD requires targeting of the infused enzyme to lysosomes within macrophages. This occurs via uptake of appropriately glycosylated enzyme to permit efficient uptake by mannose receptors on the surface of macrophages [5][6][7].…”

Section: Introductionmentioning

confidence: 99%