Glucosylsphingosine Is a Reliable Response Biomarker

Pursuing our research quest for selective and specific biomarkers we have designed and performed a research study involving potential biomarkers for Gaucher disease and we have identified glucosylsphingosine as a reliable response biomarker for this disease.

Am J Hematol. 2018 Jun;93(6):E140-E142. doi: 10.1002/ajh.25074. Epub 2018 Mar 15.

Summary

Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by impaired activity of b-glucocerebrosidase due to mutations in the GBA1 gene. While glucosylsphingosine (Lyso-Gb1), the deacylated form of glucosylceramide, is an optimal diagnostic biomarker of GD,1,2 there is a substantial lack of studies identifying a valid biomarker which quantifies patient response to therapy (rate or response biomarker).

Difficulties in identifying rate biomarkers in patients with GD are due to its diverse natural history and wide variability in patient response to therapy.

Since any disease parameter that changes with therapy potentially can serve as rate biomarker, we assessed the value of key disease parameters such as biomarkers by retrospectively analyzed data that were obtained from a homogenous population of patients. This cohort of GD patients, all non-splenectomized GD, homozygote to the nonneuronopathic N370S (c.1226A>G) mutation in the GBA1 gene and who received a low dose of enzyme replacement therapy (ERT, 15 units per kg per month), partially enabled us to overcome response variability and to assess the value of potential rate biomarkers more reliably. This study was approved by the ethics committee of Shaare Zedek Medical Center (0165-17-SZMC). See Supporting Information for detailed methods.