Glucosylsphingosine (Lyso-Gb1) — a known diagnostic biomarker of Gaucher disease — is also the most reliable response biomarker to quantify how a patient is doing while under enzyme replacement therapy (ERT), according to a retrospective study.
The study, “Glucosylsphingosine is a reliable response biomarker in Gaucher disease,” was published in the American Journal of Hematology.
Gaucher is an inherited lysosomal disorder in which a low levels of the enzyme glucocerebrosidase leads to the accumulation of two fat molecules, glucosylceramide (Gb1) and Lyso-Gb1.
Gaucher disease type 1 (GD1) is the most common form of GD, and patients often have an enlarged spleen and liver, anemia — low levels of red blood cells or hemoglobin — and low platelet levels.
While some studies have suggested Lyso-Gb1 as a good response biomarker – a way to monitor progress and improvement through treatment — heterogeneity between patients, therapies, and doses given prevent a clear demonstration of Lyso-Gb1’s value as a response biomarker.
Researchers at Hebrew University, in Jerusalem, in collaboration with Centogene, evaluated the value of key disease parameters — Lyso-Gb1 levels, platelet counts, red blood cell values, and volume of the spleen and liver — as response biomarkers by retrospectively analyzing data of 25 GD1 patients.
These patients had received a low dose of ERT (15 units per kg per month): 17 were given VPRIV, four received Cerezyme, and three received Elelyso. Disease parameters were analyzed before and during ERT, and the median follow-up time was 46 weeks.
All disease parameters improved following treatment. However, Lyso-Gb1 levels were the most reliable long-term quantitative response parameter, as it proportionally decreased during ERT.
Lyso-Gb1 levels were half-normalized after 15.4 months, while spleen volume was half-normalized at a much later point in time: 122 months.
Lyso-Gb1 levels were found to be a biomarker of spleen normalization, since a faster drop in those levels was associated with a faster spleen volume normalization.
When analyzing separately the data of patients receiving VPRIV or Cerezyme/Elelyso, VPRIV patients showed the shorter time to a half-normalization of Lyso-Gb1 levels (14.8 months), as well as of spleen volume (118 months).
These findings suggest that Lyso-Gb1 is the most reliable response biomarker, and that it has the “potential to promote resolution of persisting issues in the treatment of GD such as the optimal dose of ERT, the need to shorten the duration of clinical trials and predicting long-term organ response therapy,” the researchers wrote.