A Phase 2 Multi-center, Open-label, Switch-over Trial to Evaluate the Safety and Efficacy of Abcertin(R) in Patients with Type 1 Gaucher Disease

Gaucher disease is a lysosomal storage disease for which enzyme replacement therapy has proven to be effective. A switch-over clinical trial was performed to evaluate the efficacy and safety of Abcertin(R) (ISU Abxis, Seoul, Korea) in subjects with type 1 Gaucher disease who were previously treated with imiglucerase. Five Korean patients with type 1 Gaucher disease were enrolled. Previous doses of imiglucerase ranged from 30 to 55 U/kg every other week. The same dose of Abcertin(R) was administered to all patients for 24 weeks. Primary efficacy endpoints were changes in hemoglobin levels and platelet counts, and the secondary efficacy endpoints included changes in liver and spleen volumes, serum biomarkers, skeletal status and bone mineral density (BMD). During the study period, no statistically significant changes were observed in all parameters including hemoglobin levels and platelet counts, liver and spleen volumes, skeletal status and BMD. Abcertin(R) administration was continued in three patients for another 24 weeks as an extension of the study. Hemoglobin levels and platelet counts were maintained in all three patients. In conclusion, the efficacy and safety of Abcertin(R) are similar to those of imiglucerase, and Abcertin(R) is an effective therapeutic agent for patients with type 1 Gaucher disease (Clinical Trial Registry No. NCT02053896 at www.clinicaltrials.gov).

Quantification of glucosylceramide in plasma of Gaucher disease patients

Gaucher disease is a sphingolipidosis that leads to an accumulation of glucosylceramide. The objective of this study was to develop a methodology, based on the extraction, purification and quantification of glucosylceramide from blood plasma, for use in clinical research laboratories. Comparison of the glucosylceramide content in plasma from Gaucher disease patients, submitted to enzyme replacement therapy or otherwise, against that from normal individuals was also carried out. The glucosylceramide, separated from other glycosphingolipids by high performance thin layer chromatography (HPTLC) was chemically developed (CuSO4 / H3PO4) and the respective band confirmed by immunostaining (human anti-glucosylceramide antibody / peroxidase-conjugated secondary antibody). Chromatogram quantification by densitometry demonstrated that the glucosylceramide content in Gaucher disease patients was seventeen times higher than that in normal individuals, and seven times higher than that in patients on enzyme replacement therapy. The results obtained indicate that the methodology established can be used in complementary diagnosis and for treatment monitoring of Gaucher disease patients.

A doença de Gaucher é uma esfingolipidose caracterizada pelo acúmulo de glicosilceramida. O objetivo deste estudo foi desenvolver metodologia baseada na extração, purificação e quantificação da glicosilceramida plasmática a qual possa ser usada em laboratórios de pesquisa clínica. Após o desenvolvimento desta metodologia, foi proposto, também, comparar o conteúdo de glicosilceramida presente no plasma de pacientes com doença de Gaucher, submetidos ou não a tratamento, com aquele de indivíduos normais. A glicosilceramida, separada de outros glicoesfingolipídios por cromatografia de camada delgada de alto desempenho (HPTLC), foi revelada quimicamente (CuSO4/H3PO4) e a respectiva banda foi confirmada por imunorrevelação (anticorpo anti-glicosilceramida humana/anticorpo secundário conjudado à peroxidase). A quantificação do cromatograma por densitometria demonstrou que o conteúdo de glicosilceramida nos pacientes com doença de Gaucher era 17 vezes maior que aquele de indivíduos normais e 7 vezes maior que aquele dos pacientes com doença de Gaucher submetidos a tratamento com terapia de reposição enzimática. Os resultados obtidos demonstram que a metodologia estabelecida pode ser usada como diagnóstico complementar e como monitoração do tratamento de pacientes com doença de Gaucher.