Abstract:
:Gaucher disease (GD) is an inborn error of glycosphingolipid metabolism, associated with multisystemic manifestations resulting from the lysosomal accumulation of an incompletely degraded material (glucosylceramide) within cells of monocyte/macrophage lineage. In the majority of GD patients with non-neurological involvement (type 1), the clinical features are dominated by haematological, visceral (hepatic and splenic) and skeletal complications. Infrequently, cardiopulmonary involvement may develop and lead to major morbidity. Investigations of substrate turnover within cellular compartments, such as the lysosome, indicate that progressive tissue storage occurs when the activity of the responsible hydrolytic enzyme declines. Thus, the provision of functional enzyme to deficient cells is a straightforward means of achieving metabolic correction. Conversely, the concentration of stored substrate within cells bearing particular affected enzymes (i.e., expressing residual activity) may be controlled by a reduction of the 'load'. This means that metabolic homeostasis can also be restored by restricting the amount of substrate presented to disease cells to a level that can be hydrolysed by the existing enzyme activity. Proof-of-concept for both approaches has been demonstrated through enzyme replacement therapy using alglucerase/imiglucerase and more recently, substrate reduction therapy by miglustat. Enzyme replacement therapy is proven to be safe and effective in the treatment of GD type 1, establishing imiglucerase as the current standard of care. The experience with substrate reduction therapy, specifically miglustat, is limited but encouraging. This review is an attempt to examine the potential role of this latter approach in light of current patient management. The consideration of miglustat as a therapeutic option requires the appropriate selection of patients (amongst those unwilling or unsuitable to receive enzyme replacement therapy), a definition of the therapeutic objectives and monitoring not only for response but potential adverse effects.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Pastores GM,Barnett NLdoi
10.1517/13543784.12.2.273subject
Has Abstractpub_date
2003-02-01 00:00:00pages
273-81issue
2eissn
1354-3784issn
1744-7658journal_volume
12pub_type
杂志文章,评审abstract::Considerable progress has been made with tyrosine kinase inhibitors. After long and sustained efforts, several tyrosine kinase inhibitors with convincing in vivo experimental antitumour properties such as CP-358,774, ZD 1839, CEP-751 are entering Phase I clinical trials. Significant in vivo experimental antitumour act...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.6.771
更新日期:1997-06-01 00:00:00
abstract::Neuroimmunophilin ligands are a class of compounds that hold great promise for the treatment of nerve injuries and neurological disease. In contrast to neurotrophins (e.g., nerve growth factor), these compounds readily cross the blood-brain barrier, being orally effective in a variety of animal models of ischaemia, tr...
journal_title:Expert opinion on investigational drugs
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abstract:INTRODUCTION:Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. AREAS COVERED:We ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1513490
更新日期:2018-10-01 00:00:00
abstract::Inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) has an established role in the treatment of advanced non-small cell lung cancer. The first-generation EGFR inhibitors erlotinib and gefitinib have been approved for treatment in the second- and third-line setting. Second-generation ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2009-03-01 00:00:00
abstract::When the 'handle region' of the prorenin prosegment interacts with the (pro)renin receptor, the prorenin molecule partially changes the conformation to an enzymatically active state. On the other hand, the receptor triggers its own intracellular signalling pathways independent of the renin-angiotensin system (RAS). Th...
journal_title:Expert opinion on investigational drugs
pub_type: 社论,评审
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更新日期:2006-10-01 00:00:00
abstract::Aripiprazole has made a significant contribution to the treatment of schizophrenia and related disorders with an improved safety and tolerability profile, which has been attributed to its unique pharmacological profile. It has been claimed that partial agonism of the dopamine D(2) and 5-HT(1A) receptors and antagonism...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2007-06-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.7.799
更新日期:2004-07-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2007-08-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
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更新日期:1997-03-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.13.5.551
更新日期:2004-05-01 00:00:00
abstract::TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.6.1383
更新日期:2000-06-01 00:00:00
abstract::Sitagliptin is a once-daily, orally active, competitive and fully reversible inhibitor of dipeptidyl peptidase 4, the enzyme that is responsible for the rapid degradation of the incretin hormone glucagon-like peptide-1. It is the first in this new class of antihyperglycaemic agents to gain regulatory approval for the ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.4.533
更新日期:2007-04-01 00:00:00
abstract::Attempts to develop a vaccine against respiratory syncytial virus (RSV), the major cause of lower respiratory tract disease in infants and young children, have been unsuccessful. Passive immunisation with antibody to RSV has been found to be an effective alternative method for prophylaxis. The product currently in use...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.8.1271
更新日期:1998-08-01 00:00:00
abstract:INTRODUCTION:Studies in vitro and in vivo have identified several peptides that are potentially useful in treating systemic lupus erythematosus (SLE). The rationale for their use lies in the cost-effective production, high potency, target selectivity, low toxicity, and a peculiar mechanism of action that is mainly base...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1777983
更新日期:2020-08-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1323871
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Clusterin is a stress-induced cytoprotective chaperone protein, regulated by HSF1, and functions similarly to a small heat-shock protein. Clusterin is expressed in a variety of cancers and associated with broad-spectrum treatment resistance. Custirsen (OGX-011) is a 2'-methoxyethyl modified phosphorothioate ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780802528609
更新日期:2008-12-01 00:00:00
abstract::Overactive bladder (OAB) is a chronic distressing condition characterised by urinary urgency with or without urge incontinence, usually with frequency (voiding at least eight times daily) and nocturia. It affects millions of people worldwide independent of age, sex and race. The prevalence increases with age and is re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.9.1017
更新日期:2006-09-01 00:00:00
abstract::This paper reviews the clinical pharmacology, efficacy and safety of the novel antipsychotic drug aripiprazole. All published citations regarding aripiprazole were reviewed using a Medline((R)) search (completed for citations through mid-year, 2002). In addition, abstracts from recent scientific meetings presenting da...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.4.655
更新日期:2003-04-01 00:00:00
abstract:INTRODUCTION:Tetomilast is a novel thiazole phosphodiesterase-4 (PDE-4) inhibitor, which may prove useful in both the treatment of inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD). Here, the authors review the pharmacology of the drug, and offer critical review of the available data for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2012-12-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1299707
更新日期:2017-04-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543781003718833
更新日期:2010-04-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2008-03-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2002-08-01 00:00:00
abstract:INTRODUCTION:Due to improvements in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), several target drugs have been and are being developed. One of the possible targets in SLE is co-stimulation between antigen-presenting cells and T cells. Abatacept is a co-stimulation moderator approved for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
abstract::Bromocriptine, a potent dopamine D(2) receptor agonist, has been shown to reduce insulin resistance, glucose intolerance and hyperlipidaemia in both numerous animal studies and in Phase II studies. Bromocriptine has been used worldwide for over 20 years to treat Parkinson's disease, macroprolactinoma and other disorde...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.10.1683
更新日期:1999-10-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2009-08-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2014-10-01 00:00:00
abstract:INTRODUCTION:AEG 35156 is an antisense oligonucleotide to X-linked inhibitor of apoptosis protein (XIAP). Overexpression of XIAP is common in acute myeloid leukemia (AML) and other cancers and is thought to cause resistance to cancer therapy. Effective treatment options for patients with relapsed or refractory AML are ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.789498
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin (DMD) gene. Most patients die from respiratory failure or cardiomyopathy. There are significant unmet needs for treatments for DMD as the standard of care is principally limited to symptom relief throu...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2021.1868434
更新日期:2021-01-06 00:00:00
abstract:INTRODUCTION:Aurora kinases are key regulators of mitosis and inhibition of Aurora kinase activity is a rational therapeutic strategy in the treatment of solid tumors and hematological malignancies. AREAS COVERED:This paper will provide an updated summary of preclinical and clinical experience with ENMD-2076 in hemato...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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更新日期:2012-05-01 00:00:00