J Genet Med.  2016 Dec;13(2):59-64. 10.5734/JGM.2016.13.2.59.

Substrate reduction therapy as a new treatment option for patients with Gaucher disease type 1: A review of literatures

• Sohn YB
• Yoo HW

• KMID: 2369021
• DOI: http://doi.org/10.5734/JGM.2016.13.2.59

Abstract

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficiency of acid β-glucosidase. The diminished enzyme activity leads to the accumulation of substrates and results in multi-systemic manifestations including hepatosplenomegaly, anemia, thrombocytopenia, and bone diseases. Enzyme replacement therapy (ERT) by infusion of recombinant protein has been the standard treatment for over 20 years. Despite the successful long-term treatment with ERT, several unmet needs remain in the treatment of GD1 such as severe pulmonary and skeletal manifestations. Substrate reduction therapy (SRT) reduces the accumulation of substrates by inhibiting their biosynthesis. Eliglustat, a new oral SRT, was approved in United States and Europe as a first-line therapy for treating adult patients with GD1 who have compatible CYP2D6 metabolism phenotypes. Although eliglustat is not yet available in Korea, introduction and summary of this new treatment modality are provided in this paper by review of literatures. Despite the fact that there are only limited studies to draw resolute conclusions, the current data demonstrated that eliglustat is not inferior to ERT in terms of its clinical efficacy. The approval of eligustat enables eligible adult GD1 patients to have the option of oral therapy although it still needs further studies on long-term outcomes. The individual patient should be assessed carefully for the choice of treatment modality when eliglustat becomes available in Korea. Furthermore, the clinical guidelines for Korean patients with GD1 regarding the use of eliglustat needs to be developed in near future.

Keyword

Gaucher disease; Substrate reduction therapy; Enzyme replacement therapy; Eliglustat

MeSH Terms

Adult
Anemia
Bone Diseases
Cytochrome P-450 CYP2D6
Enzyme Replacement Therapy
Europe
Gaucher Disease*
Humans
Korea
Metabolism
Phenotype
Thrombocytopenia
Treatment Outcome
United States
Cytochrome P-450 CYP2D6