No justification for very high‐dose enzyme therapy for patients with type III Gaucher disease

Zimran, Ari; Elstein, Deborah

doi:10.1007/s10545-007-0783-8

Cited by 20 publications

(10 citation statements)

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“…154,155 Notably, no study showed any advantage of high-dose regimens when compared with the standard treatment. 154,156 Finally, studies combining ERT and SRT were initiated, based on the rationale that miglustat passes the BBB. 157 Again, the results were ambivalent.…”

Section: Gd Types 2 and 3 Because Of Its Rapid Clinical Progressionmentioning

confidence: 99%

Lysosomal storage diseases: Diagnostic confirmation and management of presymptomatic individuals

Wang

Bodamer

Watson

et al. 2011

Genetics in Medicine

206

242

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Section: Gd Types 2 and 3 Because Of Its Rapid Clinical Progressionmentioning

confidence: 99%

Lysosomal storage diseases: Diagnostic confirmation and management of presymptomatic individuals

Wang

Bodamer

Watson

et al. 2011

Genetics in Medicine

206

242

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“…ERT does not affect neurologic features (of type 3), because of its inability to penetrate the bloodbrain-barrier, even in megadoses [69]. Recently, Weinreb et al summarized the ICGG database in patients treated for 10 years, and confirmed the lasting effect alglucerase/imiglucerase treatment on haematological, visceral, and bone manifestations of GD type 1 [70].…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Gaucher Disease and Bone Manifestations

et al. 2014

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Gaucher disease is a relatively rare metabolic disease caused by the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects multiple organs, among which is the skeleton. Bone involvement occurs frequently in Gaucher disease, and is one of its most debilitating features, reducing the quality of life of patients. Bone status is an important consideration for treatment to ameliorate symptoms and reduce the risk of irreversible complications. We have conducted a systematic review of all the various aspects of Gaucher disease, focusing on different skeletal manifestations, pathophysiology of bone alterations, clinical symptoms, and current diagnostic and therapeutic approaches.

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“…[68][69][70] We have reported our ethical considerations in opposing ERT for infants with type II disease. 71 The impotence of ERT in the face of neurologic and cognitive decline in young adults with type III GD is an imperative for new modalities.…”

Section: Ert: Imiglucerasementioning

confidence: 99%

How I treat Gaucher disease

Zimran

2011

Blood

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147

135

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This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one diseasespecific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified. (Blood. 2011;118(6): 1463-1471) IntroductionThe purpose of this review is to present a cohesive approach to treating patients with Gaucher disease (GD). As can be appreciated, the spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer, in providing adequate treatment for all symptomatic patients with GD. As a treating physician dedicated to GD even before the era of enzyme replacement therapy (ERT), my mandate and inspiration has always been to provide the best therapy with the least malfeasance. Description of GDGD is one of the most common glycolipid storage disorders, caused by an inherited deficiency of the lysosomal enzyme ␤-glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. 1 Accordingly, key disease features are related to splenomegaly with hypersplenism, hepatomegaly, and bone involvement. Although a single-gene disorder, phenotypic expression is extremely variable, ranging from totally asymptomatic (only detectable by DNA analysis or enzyme deficiency) to a lethal newborn form with hydrops fetalis and ichthyosis. Many manifestations, some notuncommon and others very rare, cannot be explained by storage per se; examples include immunologic abnormalities, increased prevalence of certain malignancies with relative paucity of ...

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No justification for very high‐dose enzyme therapy for patients with type III Gaucher disease

Cited by 20 publications

References 14 publications

Lysosomal storage diseases: Diagnostic confirmation and management of presymptomatic individuals

Lysosomal storage diseases: Diagnostic confirmation and management of presymptomatic individuals

Gaucher Disease and Bone Manifestations

How I treat Gaucher disease

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