Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report

Abstract

BackgroundGaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy.Case presentationWe report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient’s spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient’s quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no adverse events have been reported.ConclusionsOral miglustat therapy proved to be a valid alternative treatment to intravenous enzyme replacement therapy for long-term maintenance in this patient with Gaucher disease type 1, who showed persistent allergic intolerance to imiglucerase infusions. This report exemplifies the type of patient with Gaucher disease type 1 who can benefit from switching from enzyme replacement therapy to substrate reduction therapy.

The Role of Dimethyl Sulfoxide (DMSO) in Gene Expression Modulation and Glycosaminoglycan Metabolism in Lysosomal Storage Disorders on an Example of Mucopolysaccharidosis

“…Implementation of this strategy is called substrate reduction therapy (SRT) [9]. The efficiency of this rationale has been observed using the flavonoid genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4 H -1-benzopyran-4-one) in Sanfilippo disease, and miglustat (Zavesca ® ) in Gaucher disease [10]. Many investigations have revealed that due to pleiotropic effects, genistein can be used to modulate pivotal mechanisms in human cells, for instance, the cell cycle [11], metabolism of macromolecules [12] or biogenesis and activity of lysosomes [13,14].…”

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach

“…ERT aids the body in recycling more waste material, specifically GlcCer, whereas SRT helps the body generate less of this waste material. SRT does not rely on enzyme replacement but instead reduces the accumulation of glycolipids by balancing the residual activity of the deficient enzyme with lowered substrate levels 123 . Recent studies have shown that SRT- oral miglustat, which also can cross BBB 124 , may be more effective than ERTs in reducing the size of the spleen and liver, improving bone density, and reducing levels of the biomarker chitotriosidase 123 .…”

“…SRT does not rely on enzyme replacement but instead reduces the accumulation of glycolipids by balancing the residual activity of the deficient enzyme with lowered substrate levels 123 . Recent studies have shown that SRT- oral miglustat, which also can cross BBB 124 , may be more effective than ERTs in reducing the size of the spleen and liver, improving bone density, and reducing levels of the biomarker chitotriosidase 123 . SRT venglustat with the potential of crossing BBB can alleviate the symptoms and prevent disease progression 125 .…”