Newly identified Player in Gaucher Disease Could be Helpful in Diagnosis, Monitoring, Study Says

Newly identified Player in Gaucher Disease Could be Helpful in Diagnosis, Monitoring, Study Says

A new protein recently identified by researchers could be used in diagnosing patients with Gaucher disease or assessing how patients are responding to therapies, a study suggests.

Chitinase-3-like 1 (CHI3L1), a protein considered a pro-inflammatory marker, was found in significantly higher levels in animal models and patients with Gaucher disease.

The study, “Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease,” was published online in the journal EBioMedicine.

Gaucher disease is a common lysosomal storage disorder caused by a deficiency in the glucocerebrosidase enzyme. However, it can manifest in different forms, suggesting that more proteins, yet unidentified, are involved in the disease process.

Researchers had previously found that the enzyme progranulin played a part in Gaucher disease. Glucocerebrosidase is found in lysosomes — structures that function as the cell’s digestive system — and progranulin is key in delivering glucocerebrosidase into these structures. Mice without this enzyme have displayed Gaucher-like symptoms, and patients often have mutations in its gene.

To find other players in Gaucher disease, researchers set out to identify proteins that worked downstream of progranulin.

This led them to CHI3L1, an enzyme of the chitinase family. Other chinitases, such as CHIT1, have already been linked to lysosomal storage disorders, including Gaucher.

Using mouse models of the disease, researchers found that CHI3L1 was present at higher levels than in healthy mice. But treating mice with progranulin — which reversed the disease symptoms — made CHI3L1 levels drop. They observed the same action in similarly treated cells removed from Gaucher disease patients.

Compared with healthy subjects, CHI3L1 was elevated in blood samples from Gaucher patients. This suggests that CHI3L1 is a potential biomarker of the disease, and measuring its levels in blood samples could be used to diagnose and monitor disease progression in patients.

More studies are required to validate the use of CHI3L1 as a biomarker and to evaluate whether it is superior to existing biomarkers, researchers said.

“Identification and characterization of this new molecule in [Gaucher disease] may lead to innovative diagnostic biochemical approaches for [lysosomal storage disorder], in particular [Gaucher disease]. Additionally, this factor may be also employed as a biomarker for evaluating the therapeutic effects of new treatments,” they conclude.