Lipid Storage Disorders Medication

Updated: Jun 10, 2020
  • Author: Rubia Khalak, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
  • Print

Medication Summary

Recombinant enzymes may be used to treat Gaucher and Fabry disease. Glucosylceramide synthase inhibitors are used for adults with type 1 Gaucher disease. For more information, see the Medscape Reference articles Gaucher Disease and Fabry Disease.


Enzyme replacement therapies

Class Summary

Specific recombinant enzymes are available to treat Gaucher and Fabry Disease.

Imiglucerase is approved for children aged 2 years or older for Gaucher disease. Velaglucerase and taliglucerase are both approved for children aged 4 years or older for Gaucher disease.

Imiglucerase (Cerezyme)

A recombinant-derived analog of beta-glucocerebrosidase. It is an enzyme used for replacement therapy in type 1 Gaucher disease. Catalyzes hydrolytic cleavage of glucocerebroside (a glycoprotein) to glucose and ceramide within the lysosomes of phagocytic cells in the reticuloendothelial system. This normally is a catabolic pathway of membrane lipids derived from hematologic cell turnover. A deficiency of this enzyme results in accumulation of glucocerebroside within tissue macrophages, which become engorged with the glycolipid. Treatment improves anemia and thrombocytopenia, reduces spleen and liver size, and decreases cachexia.

Velaglucerase alfa (VPRIV)

Hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long-term enzyme replacement therapy for type 1 Gaucher disease. Improves symptoms associated with the disease, including anemia, thrombocytopenia, increased spleen and liver size, and cachexia.

Taliglucerase alfa (Elelyso)

Taliglucerase is a plant-based recombinant enzyme for type I Gaucher disease. It catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, which results in reduced spleen and liver enlargement and increased RBCs and platelets.

Agalsidase alfa (Fabrazyme, Replagal)

Recombinant form of the human enzyme alpha-galactosidase A, levels of which are deficient in Fabry disease. Data from clinical trials show a decrease in GL-3 levels following enzyme replacement, reversal in lipid tissue storage, stabilized or improved renal and cardiac function, and reduced or relief from neuropathic pain. Following enzyme replacement, the long-term use of neuropathic pain medication has been reduced.

Both agalsidase beta and alpha forms are designated as orphan drugs. Agalsidase beta (Fabrazyme) is manufactured by Genzyme Corporation (Cambridge, Mass) and is based on expression of the human GLA gene in CHO cells.

Agalsidase alfa (Replagal) is manufactured by Transkaryotic Therapies, Inc (Cambridge, Mass) and is based on activation of the human GLA gene expression in human (skin) fibroblasts.


Glucosylceramide Synthase Inhibitors

Class Summary

These agents are indicated for type 1 Gaucher disease. These agents inhibit the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions that result in the synthesis of most glycosphingolipids, including glucocerebroside. The goal of treatment is to reduce the rate of glucocerebroside biosynthesis so that the amount is reduced to a level that allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy).

Eliglustat (Cerdelga)

Eliglustat is a specific inhibitor of glucosylceramide synthase, thereby reducing production of glucosylceramide. It is indicated for the long-term treatment of adults with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EM), intermediate metabolizers (IM), or poor metabolizers (PM) as detected by an FDA-cleared test for phenotype. Dosage is based on establishing the patient's CYP2D6 metabolizer status.

Miglustat (Zavesca)

Indicated for type 1 Gaucher disease in patients in whom ERT is not a therapeutic option. Reduces GSL production by inhibiting glucosylceramide synthase. Reduces spleen and liver volume and increases hemoglobin and platelet counts.