FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2553365471> ?p ?o ?g. }

• W2553365471 abstract "Abstract Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme β-glucocerebrosidase (GCase). Deficient GCase activity leads to symptoms such as anemia, thrombocytopenia, hepatosplenomegaly, bone necrosis, infarcts and osteoporosis, and in some cases, neuropathic disease. The pharmacological chaperone AT2101 (isofagamine tartrate) selectively binds and stabilizes GCase in the ER and increases trafficking of the enzyme to the lysosome. In single- and repeat-dose Phase 1 clinical trials involving 72 healthy volunteers, AT2101 was well tolerated with no serious adverse events. In the repeat-dose study, a dose-dependent increase in GCase levels in white blood cells (up to 3.5-fold) was observed during the 7 day treatment period, and enzyme levels remained elevated for more than a week after removal of the drug. To evaluate the effects of AT2101 on a range of different GCase variants, we conducted an ex vivo response study using macrophages and EBV-transformed lymphoblasts derived from GD patients. The study was conducted on samples from 53 patients enrolled at 5 sites in the United States. The study included 26 males and 26 females with type I GD, and one male with type III GD. Patients ranged in age from 7 to 83 years; 50 of 53 patients were receiving imiglucerase and blood was drawn prior to enzyme infusion. Incubation of cells with AT2101 (5 days) increased GCase levels in macrophages or lymphoblasts derived from 52 of 53 patients representing 18 different genotypes (mean: 2.6-fold, range: 1.4- to 8.6-fold). Plasma was also screened for potential biomarkers associated with inflammation, bone metabolism, multiple myeloma and neurodegeneration. Analysis of 40 markers showed elevated levels of chitotriosidase activity, TRACP 5b, PARC, IL-8, IL-17, VEGF, MIP-1α and α-synuclein and reduced bone-specific alkaline phosphatase levels in some patients. These results show that an imbalance between osteoclast and osteoblast activities may remain even though treatment with imiglucerase (Wenstrup et al. 2007. Journal of Bone and Mineral Research, 22: 119–26) and bisphosphonates (Wenstrup et al. 2004. Blood, 104: 1253–7) have been shown to increase bone mass in GD patients. Interestingly, increases in IL-8, IL-17, VEGF, MIP-1α, impaired osteoblast activity and increased osteoclast activity have also been implicated in the pathogenesis of multiple myeloma, and it has been reported that GD patients have an increased risk of developing multiple myeloma (Rosenbloom et al. 2005. Blood, 105: 4569–72). To determine if these biomarkers respond to treatment with AT2101, they are being monitored in an ongoing 6-month Phase 2 clinical trial with AT2101 in GD patients. Additionally, a 4-week Phase 2 clinical trial with AT2101 is being conducted in GD patients and preliminary results are expected by the end of 2007." @default.
• W2553365471 created "2016-11-30" @default.
• W2553365471 creator A5020371999 @default.
• W2553365471 creator A5030024227 @default.
• W2553365471 creator A5034612091 @default.
• W2553365471 creator A5035799189 @default.
• W2553365471 creator A5036564166 @default.
• W2553365471 creator A5054568032 @default.
• W2553365471 creator A5059655140 @default.
• W2553365471 creator A5061182342 @default.
• W2553365471 creator A5076685655 @default.
• W2553365471 creator A5084708134 @default.
• W2553365471 creator A5088745449 @default.
• W2553365471 creator A5090039213 @default.
• W2553365471 date "2007-11-16" @default.
• W2553365471 modified "2023-09-30" @default.
• W2553365471 title "Pharmacological Chaperone Therapy for the Treatment of Gaucher Disease: Results of Phase 1 Clinical Trials and a Clinical Ex Vivo Response Study with a Survey of Blood Markers for 53 Gaucher Patients." @default.
• W2553365471 doi "https://doi.org/10.1182/blood.v110.11.2404.2404" @default.
• W2553365471 hasPublicationYear "2007" @default.
• W2553365471 type Work @default.
• W2553365471 sameAs 2553365471 @default.
• W2553365471 citedByCount "1" @default.
• W2553365471 countsByYear W25533654712019 @default.
• W2553365471 crossrefType "journal-article" @default.
• W2553365471 hasAuthorship W2553365471A5020371999 @default.
• W2553365471 hasAuthorship W2553365471A5030024227 @default.
• W2553365471 hasAuthorship W2553365471A5034612091 @default.
• W2553365471 hasAuthorship W2553365471A5035799189 @default.
• W2553365471 hasAuthorship W2553365471A5036564166 @default.
• W2553365471 hasAuthorship W2553365471A5054568032 @default.
• W2553365471 hasAuthorship W2553365471A5059655140 @default.
• W2553365471 hasAuthorship W2553365471A5061182342 @default.
• W2553365471 hasAuthorship W2553365471A5076685655 @default.
• W2553365471 hasAuthorship W2553365471A5084708134 @default.
• W2553365471 hasAuthorship W2553365471A5088745449 @default.
• W2553365471 hasAuthorship W2553365471A5090039213 @default.
• W2553365471 hasConcept C126322002 @default.
• W2553365471 hasConcept C150903083 @default.
• W2553365471 hasConcept C197934379 @default.
• W2553365471 hasConcept C203014093 @default.
• W2553365471 hasConcept C207001950 @default.
• W2553365471 hasConcept C26291073 @default.
• W2553365471 hasConcept C2778248108 @default.
• W2553365471 hasConcept C2779134260 @default.
• W2553365471 hasConcept C2779440204 @default.
• W2553365471 hasConcept C2779969927 @default.
• W2553365471 hasConcept C2780674200 @default.
• W2553365471 hasConcept C71924100 @default.
• W2553365471 hasConcept C86803240 @default.
• W2553365471 hasConcept C90924648 @default.
• W2553365471 hasConceptScore W2553365471C126322002 @default.
• W2553365471 hasConceptScore W2553365471C150903083 @default.
• W2553365471 hasConceptScore W2553365471C197934379 @default.
• W2553365471 hasConceptScore W2553365471C203014093 @default.
• W2553365471 hasConceptScore W2553365471C207001950 @default.
• W2553365471 hasConceptScore W2553365471C26291073 @default.
• W2553365471 hasConceptScore W2553365471C2778248108 @default.
• W2553365471 hasConceptScore W2553365471C2779134260 @default.
• W2553365471 hasConceptScore W2553365471C2779440204 @default.
• W2553365471 hasConceptScore W2553365471C2779969927 @default.
• W2553365471 hasConceptScore W2553365471C2780674200 @default.
• W2553365471 hasConceptScore W2553365471C71924100 @default.
• W2553365471 hasConceptScore W2553365471C86803240 @default.
• W2553365471 hasConceptScore W2553365471C90924648 @default.
• W2553365471 hasLocation W25533654711 @default.
• W2553365471 hasOpenAccess W2553365471 @default.
• W2553365471 hasPrimaryLocation W25533654711 @default.
• W2553365471 hasRelatedWork W1992799459 @default.
• W2553365471 hasRelatedWork W2001790593 @default.
• W2553365471 hasRelatedWork W2021525329 @default.
• W2553365471 hasRelatedWork W2042557135 @default.
• W2553365471 hasRelatedWork W2084599635 @default.
• W2553365471 hasRelatedWork W2281150386 @default.
• W2553365471 hasRelatedWork W2419618477 @default.
• W2553365471 hasRelatedWork W2891948505 @default.
• W2553365471 hasRelatedWork W2990639370 @default.
• W2553365471 hasRelatedWork W43278327 @default.
• W2553365471 isParatext "false" @default.
• W2553365471 isRetracted "false" @default.
• W2553365471 magId "2553365471" @default.
• W2553365471 workType "article" @default.