Effective treatment of an elderly patient with Gaucher's disease and Parkinsonism: A case report of 24 months’ oral substrate reduction therapy with miglustat

Hughes, D.A.; Ginsberg, Lionel; Baker, Robert J.; Goodwin, S; Milligan, A; Richfield, L; Mehta, Atul

doi:10.1016/j.parkreldis.2006.07.010

Cited by 13 publications

(6 citation statements)

References 8 publications

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“…It was recently suggested that, apart from the accumulation of glucocerebroside, the degree of proteasomal degradation of misfolded glucocerebrosidase correlates with the severity of the disease (Ron & Horowitz, 2005). A commentary has claimed that this might have an impact upon cellular function and affect carcinogenesis (Hughes et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Malignancies and monoclonal gammopathy in Gaucher disease; a systematic review of the literature

et al. 2013

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SummaryGaucher disease is an autosomal, recessively inherited, lysosomal storage disease, which has been associated with gammopathies and malignancies. This report represents the results of a systematic review of the literature on the prevalence of monoclonal gammopathies and malignancies in Gaucher disease. A PubMed search identified 365 studies, of which 80 reported on concomitant Gaucher disease and malignancies and/or gammopathies (15 cohort/cross sectional studies, and 65 case reports/series). Based on these studies, we conclude that compared to the general population, Gaucher patients have an increased risk of cancer in general [pooled relative risk of 1Á70 (95% confidence interval 1Á27-2Á31)], and multiple myeloma and haematological malignancies in particular (estimated risk between 25Á0 and 51Á1 and 3Á5 and 12Á7, respectively). In addition, an increased risk has been reported for hepatocellular carcinoma and renal cell carcinoma. Several factors have been hypothesized to play a role in the pathophysiology. These include: splenectomy, immune dysregulation, endoplasmic reticulum stress, genetic modifiers, altered iron metabolism and insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Malignancies and monoclonal gammopathy in Gaucher disease; a systematic review of the literature

et al. 2013

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“…Comparably fewer data are available relating to miglustat in GD1, and the evidence regarding the efficacy of miglustat has been drawn mainly from clinical trials and published reports of its use in practice [16][17][18]20,59 . In total, data on the efficacy of miglustat presented in this review are based on over 120 GD1 patients and safety data on over 200 patients [16][17][18]20,21,42,54,55,59 , There are limited data available on naïve patients treated with miglustat, as all three non-comparative, open-label trials (and the extension studies) enrolled a proportion of patients who had previously received ERT [16][17][18]59 . Furthermore, case reports of the effects of miglustat included patients switched from ERT 42,54 .…”

Section: Discussionmentioning

confidence: 99%

“…Since the publication of the EWGGD report 58 , further data on the efficacy of miglustat in mild to moderate GD1 patients have become available from more recent clinical trials 18,21 and from 'real-world' cohort studies (clinical site experience using the commercial drug) and case reports 20,42,54 . Data from these reports provide guidance on the attainment of therapeutic goals in GD1 patients on miglustat (Table 3).…”

Section: Tolerabilitymentioning

confidence: 99%

Goal-oriented therapy with miglustat in Gaucher disease

Pastores

Giraldo

Chérìn

et al. 2008

Current Medical Research and Opinion

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“…Early reports of GD1 patients with parkinsonism were quick to note that neurological symptoms did not improve with enzyme replacement 12-14 . Another case report later showed that miglustat, which treats GD1 by lowering elevated substrates of glucocerbrosidase, was tolerated by a patient with GD1 and parkinsonism 70 , although the suggestion that miglustat might have stabilized his neurological condition caused some contention 71 , as miglustat does not readily cross the blood-brain barrier. Recently, investigation in mouse models of GD1-PD found that viral-vector-mediated replacement of normal GBA genes in the CNS resulted in expression of normal ß-glucocerebrosidase in brain tissue, improvement in memory function when virus was delivered to the hippocampus, and slowing of the rate of α-synuclein accumulation compared to mice administered a control virus 72 .…”

Section: Pathogenesis Of Gba-pd and Its Implications For Treatmentmentioning

confidence: 99%

The Association Between ß-Glucocerebrosidase Mutations and Parkinsonism

Swan

Saunders‐Pullman

2013

Curr Neurol Neurosci Rep

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Mutations in the ß-glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme ß-glucocerebrosidase, have traditionally been implicated in Gaucher disease, an autosomal-recessive lyososomal storage disorder. Yet the past two decades have yielded an explosion of epidemiological and basic-science evidence linking mutations in GBA with the development of Parkinson disease as well. Although the specific contribution of mutant GBA to the pathogenesis of parkinsonism remains unknown, evidence suggests both loss of function and toxic gain-of-function by abnormal ß-glucocerebrosidase may be important, and a close relationship between ß-glucocerebrosidase and α-synuclein. Furthermore, multiple lines of evidence suggest that while GBA-associated PD closely mimics idiopathic PD (IPD), it may present at a younger age, and is more frequently complicated by cognitive dysfunction. Understanding the clinical association between GBA and PD, and the relationship between ß-glucocerebrosidase and α-synuclein, may enhance understanding of the pathogenesis of IPD, improve prognostication and treatment of GBA carriers with parkinsonism, and may furthermore inform therapies for IPD not due to GBA mutations.

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Effective treatment of an elderly patient with Gaucher's disease and Parkinsonism: A case report of 24 months’ oral substrate reduction therapy with miglustat

Cited by 13 publications

References 8 publications

Malignancies and monoclonal gammopathy in Gaucher disease; a systematic review of the literature

Malignancies and monoclonal gammopathy in Gaucher disease; a systematic review of the literature

Goal-oriented therapy with miglustat in Gaucher disease

The Association Between ß-Glucocerebrosidase Mutations and Parkinsonism

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