Enzyme Replacement for Lysosomal Diseases

Abstract

Following the demonstration of the nature of the enzymatic defects in the sphingolipid storage disorders in the mid-1960s, consideration was directed to the development of therapy for patients with these conditions. High on the list of possibilities was enzyme supplementation or replacement. Many years of arduous investigation and the development of novel protein targeting strategies were required to bring this concept to fruition. Enzyme replacement therapy (ERT) was eventually shown to be extraordinarily effective for patients with Gaucher disease, the most prevalent metabolic storage disorder of humans. Demonstration of the benefit of ERT in this disorder led to the extension of this approach to the treatment of other lysosomal storage disorders. This review presents the current status and anticipated developments in this field.

Nephrotic Syndrome Caused by Immune-Mediated Acquired LCAT Deficiency

“…12 Recently, enzyme replacement therapy was shown to be effective for certain lysosomal diseases. 19 FLD could be an attractive candidate for enzyme replacement therapy, because LCAT acts in the plasma compartment, without any organspecific distribution. 20 In mouse models of LCAT deficiency, human recombinant LCAT treatment rapidly restored the normal lipoprotein phenotype in LCAT-knockout mice, and increased the cholesterol efflux.…”

Selective Screening for Lysosomal Storage Diseases with Dried Blood Spots Collected on Filter Paper in 4,700 High-Risk Colombian Subjects

“…Given that in the recent years a number of treatments are available to treat some of these diseases, diagnosis becomes relevant. This point is especially important in the case of enzyme replacement therapy for disorders such as Fabry, Gaucher, Pompe, and Mucopolysaccharidosis type I, II, and VI for which an early diagnosis could dramatically improve the outcome of the disease (Brady 2006).…”

Velaglucerase alfa

“…Although enzyme replacement therapy (ERT) for lysosomal storage disorders, such as Gaucher's disease, was proposed in the 1960s, producing sufficient quantities of β-glucocerebrosidase and targeting it to the appropriate cells proved challenging 2 . Based on an understanding of the importance of the mannose receptor on the surface of macrophages in enzyme internalization, placenta-derived β-glucocerebrosidase, processed to expose mannose chains to promote recognition by macrophages, was developed 2,3 .…”

“…Based on an understanding of the importance of the mannose receptor on the surface of macrophages in enzyme internalization, placenta-derived β-glucocerebrosidase, processed to expose mannose chains to promote recognition by macrophages, was developed 2,3 . Injection of such a β-glucocerebrosidase product, alglucerase (Ceredase; Genzyme), improved key disease characteristics, such as low haemoglobin concentrations in patients with Gaucher's disease 2,3 , which led to its approval by the US Food and Drug Administration (FDA) in 1991.…”

“…ERT is now the standard of care for symptomatic type 1 Gaucher's disease 1,2 . Imiglucerase (Cerezyme; Genzyme), a recombinant analogue of β-glucocerebrosidase produced in Chinese hamster ovary cells 2,4 , was approved by the FDA in 1994 and largely replaced alglucerase.…”