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Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease.

Bennett LL, Turcotte K - Drug Des Devel Ther (2015)

Bottom Line: GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia.GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3) which are more progressive diseases with no approved drugs available at this time.Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Union University, Jackson, TN, USA.

ABSTRACT
The purpose of this article is to review eliglustat tartrate, a substrate reduction therapy, for the treatment of Gaucher disease type 1 (GD1). GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia. GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3) which are more progressive diseases with no approved drugs available at this time. Treatment options for GD1 include enzyme replacement therapy and substrate reduction therapy. Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome. Eliglustat was approved by the US Food and Drug Administration after three Phase I, two Phase II, and two Phase III clinical trials. The dose of eliglustat is 84 mg twice a day or once daily depending on the cytochrome P450 2D6 genotype of the patient.

No MeSH data available.


Related in: MedlinePlus

Synthesis of glycosphingolipids. In Gaucher disease, glucosylceramide accumulates due to a decrease or loss of activity of β-glucocerebrosidase. Eliglustat tartrate blocks the enzyme glucosylceramide synthase. Glucosylceramide synthase is localized in the cis/medial Golgi membrane which plays an important role in catalyzing the formation of glucosylceramide from ceramide and UDP-glucose. Glucosylceramide is further metabolized to other glycosphingolipids (not shown).
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f1-dddt-9-4639: Synthesis of glycosphingolipids. In Gaucher disease, glucosylceramide accumulates due to a decrease or loss of activity of β-glucocerebrosidase. Eliglustat tartrate blocks the enzyme glucosylceramide synthase. Glucosylceramide synthase is localized in the cis/medial Golgi membrane which plays an important role in catalyzing the formation of glucosylceramide from ceramide and UDP-glucose. Glucosylceramide is further metabolized to other glycosphingolipids (not shown).

Mentions: The two small molecule SRTs available, ie, miglustat and the newer eliglustat tartrate, are taken as oral drugs. In contrast with ERTs, which aim to replace the defective enzyme with active enzyme, SRTs work by inhibiting UDP-GLC synthase, the first enzyme catalyzing the biosynthesis of glycosphingolipids from UDP-glucose and ceramide, thus reducing the influx of GLC into the lysosome. Figure 1 shows the pathway for synthesis of glycosphingolipids and where eliglustat works.52,53


Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease.

Bennett LL, Turcotte K - Drug Des Devel Ther (2015)

Synthesis of glycosphingolipids. In Gaucher disease, glucosylceramide accumulates due to a decrease or loss of activity of β-glucocerebrosidase. Eliglustat tartrate blocks the enzyme glucosylceramide synthase. Glucosylceramide synthase is localized in the cis/medial Golgi membrane which plays an important role in catalyzing the formation of glucosylceramide from ceramide and UDP-glucose. Glucosylceramide is further metabolized to other glycosphingolipids (not shown).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554398&req=5

f1-dddt-9-4639: Synthesis of glycosphingolipids. In Gaucher disease, glucosylceramide accumulates due to a decrease or loss of activity of β-glucocerebrosidase. Eliglustat tartrate blocks the enzyme glucosylceramide synthase. Glucosylceramide synthase is localized in the cis/medial Golgi membrane which plays an important role in catalyzing the formation of glucosylceramide from ceramide and UDP-glucose. Glucosylceramide is further metabolized to other glycosphingolipids (not shown).
Mentions: The two small molecule SRTs available, ie, miglustat and the newer eliglustat tartrate, are taken as oral drugs. In contrast with ERTs, which aim to replace the defective enzyme with active enzyme, SRTs work by inhibiting UDP-GLC synthase, the first enzyme catalyzing the biosynthesis of glycosphingolipids from UDP-glucose and ceramide, thus reducing the influx of GLC into the lysosome. Figure 1 shows the pathway for synthesis of glycosphingolipids and where eliglustat works.52,53

Bottom Line: GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia.GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3) which are more progressive diseases with no approved drugs available at this time.Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Union University, Jackson, TN, USA.

ABSTRACT
The purpose of this article is to review eliglustat tartrate, a substrate reduction therapy, for the treatment of Gaucher disease type 1 (GD1). GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia. GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3) which are more progressive diseases with no approved drugs available at this time. Treatment options for GD1 include enzyme replacement therapy and substrate reduction therapy. Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome. Eliglustat was approved by the US Food and Drug Administration after three Phase I, two Phase II, and two Phase III clinical trials. The dose of eliglustat is 84 mg twice a day or once daily depending on the cytochrome P450 2D6 genotype of the patient.

No MeSH data available.


Related in: MedlinePlus