A new model for predicting the risk of long-term complications in patients with type 1 Gaucher disease (GD) was designed based on a 17-year study that measured a naturally-occurring enzyme that is a marker of GD activity (chitotriosidase) before and after the start of enzyme replacement therapy (ERT).
The study, “Modelling long-term evolution of chitotriosidase in non-neuronopathic Gaucher disease,” was published in the Scandinavian Journal of Clinical and Laboratory Investigation by a team of researchers at the University of Medicine and Pharmacy in Romania.
Non-neuronopathic (type 1) GD is characterized by hepatosplenomegaly (enlargement of the liver and spleen), haematological abnormalities (abnormalities in the blood and blood-forming organs) and bone problems.
Non-neuronopathic GD is now treated either with enzyme replacement therapy (ERT), or with substrate reduction therapy (SRT).
In Romania, splenectomy (surgical removal of the spleen) was used often before ERT became available in order to minimize the consequences of an enlarged spleen. ERT and SRT involve lifelong treatment with expensive drugs, and accurate monitoring of disease activity is recommended by the International Collaborative Gaucher Group Registry.
Plasma chitotriosidase has been widely used for the evaluation and follow-up of GD patients, as it presents high levels in untreated patients and quickly responds to successful treatments.
Researchers for this study stated that they aimed “to develop a more accurate model, depicting the evolution of chitotriosidase during the whole evaluation period, comprising both the interval from diagnosis until the start of ERT and from this moment until the closing date.”
For 17 years, 55 patients (23 males and 32 females) with non-neuronopathic (type 1) GD were tested regularly for chitotriosidase activity in their blood. The average chitotriosidase values were consistently high before ERT, then dropped dramatically during the first years of treatment, finally leveling out after the third year.
A clear difference was seen between patients who had splenectomies and those who did not. Those who had the procedure presented lower chitotriosidase activities before the start of ERT and higher values after long-term ERT. The same was observed in patients with bone complications.
“Splenectomy and the occurrence of bone complications significantly delayed the decline in chitotriosidase activity and induced higher mean residual values after long-term (4-9 years) ERT,” the researchers wrote.
Chitotriosidase levels in patients diagnosed before the age of 15 were lower before the start of ERT than in patients diagnosed later, and higher residual values.
“Circulating chitotriosidase remains, in our view, an interesting and informative biomarker of GD, being still used by many laboratories for patient monitoring, especially during ERT,” the authors wrote.
“… one can predict chitotriosidase variation and estimate the risk for long-term complications in different patient subgroups, for a better therapeutic management during enzyme supplementation. Our model highlights the differences in patient responsiveness to ERT, whose implications in the pathophysiology [disease progress] of GD deserve further investigation,” they concluded.