Study Compares Biochemical Outcomes of Gaucher Disease Type 1 Patients to Selected Therapies

Study Compares Biochemical Outcomes of Gaucher Disease Type 1 Patients to Selected Therapies

The biochemical responses in patients with Gaucher disease type I (GD1) treated with some selected therapeutic options have been compared in a study, “Biochemical response to substrate reduction therapy versus enzyme replacement therapy in Gaucher disease type 1 patients,” published in Orphanet J Rare Dis.

A deficient glucocerebrosidase enzyme caused by a mutant glucocerebrosidase gene is responsible for the development of GD1. This results in accumulation of lipid-laden macrophages that leads to numerous health issues, including swelling of the liver and spleen, reduction in the number of blood cells, and debilitating bone complications.

Several therapeutic approaches have been tested for GD1. The two most important ones are the enzyme replacement therapy (ERT) based on recombinant human acid β-glucosidase, and the substrate reduction therapy (SRT) believed to function through inhibition of glucosylceramide synthase.

“Until now a direct comparison of effects on biochemical markers reflecting disease burden between the aforementioned SRT and ERT treatment modalities has not been available,” the authors wrote.

In this study, the researchers compared biochemical responses in patients with GD1 treated with glycosphingolipid synthesis inhibitors miglustat and eliglustat and ERT.

A total of 17 patients with GD1 participated in the study. Six patients received eliglustat, two of whom were switched from ERT; nine received miglustat, with seven switchers; and four were treated with ERT (median dose 60U/kg/m). They were then evaluated for plasma protein markers indicative of disease burden (chitotriosidase, CCL18) and lipids reflecting substrate accumulation (glucosylsphingosine, glucosylceramide).

Other measurements related to the liver and spleen sizes, platelets, hemoglobin, and fat fraction were carried out and compared.

The results suggested that both eliglustat and ERT therapies reduced levels of chitotriosidase, CCL18, and glucosylsphingosine in patients naïve to treatment at comparable rates, and a lesser response was obtained with miglustat. The average recorded chitotriosidase in naïve patients after two years of therapy have declined by 89 percent, 88 percent, and 37 percent for eliglustat, ERT, and miglustat, respectively. Meanwhile, CCL18 has declined by  73 percent, 54 percent, and 10 percent; and glucosylsphingosine by 86 percent, 78 percent, and 48 percent for eliglustat, ERT and miglustat, respectively.

Four patients receiving eliglustat had plasma glucosylceramide levels inferior to the normal range in 20 healthy controls. A diminution or stabilization in the biochemical markers was noticed in two patients who switched from ERT to eliglustat, but lower for seven patients who switched to miglustat. Finally, clinical parameter outcomes upon treatment with eliglustat were comparable with those of ERT.

“Our explorative study provides evidence that biochemical markers respond comparably in patients receiving eliglustat treatment and ERT, while the corresponding response to miglustat treatment is less. Our present biochemistry and clinical findings should be extended by studies with larger cohorts,” the researchers concluded.

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