Recently Identified Biomarker Could Be Valid Diagnostic Tool for Gaucher Disease, Mouse Study Suggests

Recently Identified Biomarker Could Be Valid Diagnostic Tool for Gaucher Disease, Mouse Study Suggests

Glucosylsphingosine (lyso-Gb1), a recently identified biomarker for Gaucher disease (GD), was shown to contribute to the development or peripheral symptoms in a mouse study, potentially validating its use as a diagnostic tool, according to new research.

The study, “Glucosylsphingosine Causes Hematological and Visceral Changes in Mice—Evidence for a Pathophysiological Role in Gaucher Disease,” was published in the International Journal of Molecular Sciences.

Biomarkers in GD are very useful for diagnosis, monitoring the progression of the disease, and assessing the effectiveness of therapeutic strategies. While several biomarkers, including chitotriosidase activity and the chemokine CCL18, have been identified, none of them have been linked to the primary disease and are only a result of secondary issues due to Gaucher disease.

Patients with Gaucher tend to have an accumulation of a compound called lyso-Gb1. GD patients can either have neuronopathic GD, which refers to disease in the brain, or non-neuronopathic GD.

Patients with neuronopathic GD tend to have high levels of lyso-Gb1 in their brains compared to those with non-neuropathic GD, indicating that lyso-Gb1 may play a role in brain disease. Interestingly, lyso-Gb1 is also highly elevated in the plasma of all GD patients.

Current methods, such as liquid chromatography-tandem mass spectrometry (LC–MS/MS), are able to accurately detect lyso-Gb1 in patient serum samples, so it has become an increasingly used biomarker to detect GD.

German researchers set out to determine the role of lyso-Gb1 in the development of this disease to further validate its use as a biomarker.

They used genetically normal mice and continuously administered lyso-Gb1 at a dose of 10 mg·kg−1 per day. The mice were routinely checked for blood lyso-Gb1 levels using the LC–MS/MS system. The mice showed up to a 500-fold increase in lyso-Gb1 levels, which is similar to those seen in moderately to severely affected patients.

Researchers also demonstrated that lyso-Gb1 gathered in the peripheral tissue, similar to humans with Gaucher disease. Peripheral tissue, in this case, refers to organs such as the liver and the spleen.

Results from the study showed decreased levels of hemoglobin and red blood cells, indicating the mice had mild anemia. They also showed higher spleen weights and a slight inflammatory response after eight weeks of treatment.

These results demonstrated that lyso-Gb1 is involved in the peripheral tissue and blood cell response in mice, which led to the development of peripheral symptoms of GD.

“Taken together, these findings demonstrate that lyso-Gb1 replicates a number of the molecular characteristics of a GD type 1, demonstrating its usefulness for further studies as a toxicological disease model,” the authors concluded.