Biomarker could signal when to start Gaucher type 1 treatment
Study: Lyso-GL1 level may also differentiate treated, untreated patients
Measuring the amount of glucosylsphingosine, also called lyso-Gb1, a key marker used to help diagnose Gaucher disease, may aid doctors in deciding when someone with Gaucher disease type 1 should begin treatment, a new study suggests.
Additionally, a certain level of lyso-GL1 may help distinguish between patients who are undergoing treatment and those who are not.
According to researchers, “the predictive performance of this identified threshold was comparable to that reported in a previous study, underscoring the reproducibility and potential utility of lyso-[Gb1] as a reliable and objective biomarker to guide treatment initiation in Gaucher disease.”
The study, “Correlation of Plasma Lyso-GL1 Levels with Clinical Phenotype and Treatment Decisions in Patients with Gaucher Disease,” was published in Molecular Genetics and Metabolism.
Guidelines for starting treatment lacking
Gaucher disease is caused by mutations in the GBA1 gene, resulting in the dysfunction or absence of the glucocerebrosidase enzyme and the accumulation of the fatty molecules glucocerebroside (Gb1) and glucosylsphingosine (lyso-Gb1). This leads to disease symptoms such as enlarged spleen and liver, fatigue due to low red blood cell levels, easy bruising and bleeding due to low platelet levels, and bone problems.
The disease’s management may be complicated by symptom variability and the lack of standardized guidelines for starting treatment. As such, “determining the optimal timing for treatment initiation … is crucial, as early intervention can prevent irreversible disease complications,” the researchers wrote.
To evaluate whether the levels of lyso-Gb1 could inform treatment decisions, researchers at the Icahn School of Medicine at Mount Sinai in New York retrospectively analyzed data from 240 individuals with Gaucher disease.
Most participants were adults (80.8%), while 19.2% were pediatric patients at the time of the first lyso-Gb1 measurement. Almost all had type 1 Gaucher disease (97.5%).
Overall, 164 patients (68.3%) were treated at a median age of 33 years and followed up for about three years. At baseline, defined as the first lyso-Gb1 level evaluation, 74.4% of patients were receiving enzyme replacement therapy (ERT), primarily Cerezyme (imiglucerase), while 25.6% were treated with substrate reduction therapy (SRT).
Patients divided into pre-treatment, post-treatment, untreated groups
Participants were divided into three groups: those who started treatment before a first lyso-Gb1 measurement (pre-lyso-Gb1, 57.9%), patients who began treatment after one or more lyso-Gb1 measurements, and thus had pre-treatment data (post-lyso-Gb1, 10.4%), and untreated participants (31.7%).
After the first lyso-Gb1 evaluation, most patients remained on the same treatment regimen, while 16 participants switched from ERT to SRT, and three switched from SRT to ERT.
According to the researchers, the more common transition from ERT to SRT “is consistent with the practical advantage of oral medication over biweekly infusions in terms of convenience and ease of administration.”
Participants in the post-lyso-Gb1 group had a median lyso-Gb1 level of 91.6 nanograms per milliliter (ng/mL) before starting treatment, which significantly decreased to 19.5 ng/mL at the last evaluation. In the untreated group, median lyso-Gb1 levels increased from 14.2 ng/mL to 17 ng/mL, while in the pre-lyso-Gb1 group, they remained stable (4.5 ng/mL vs. 3.5 ng/mL).
“As expected, the highest lyso-[Gb1] levels were observed in the treated post-lyso-[Gb1] cohort, which consisted of patients who started treatment during the study period due to emerging symptoms and disease progression,” the researchers wrote.
Lyso-Gb1 levels positively correlated with those of disease activity marker
The levels of lyso-Gb1 were positively correlated with the levels of chitotriosidase, a marker of Gaucher disease activity, across the three patient groups. In untreated patients, lyso-Gb1 levels were also positively linked to spleen volume.
Additionally, higher lyso-Gb1 levels were associated with lower hemoglobin levels in the post-lyso-Gb1 treatment group and with reduced platelet counts among untreated patients. Hemoglobin is the protein that carries oxygen in red blood cells.
Further analysis demonstrated that a lyso-Gb1 cutoff value of 78.9 ng/mL could distinguish between patients with Gaucher disease who were receiving treatment and those who were not, with an accuracy of 86.5%.
According to the researchers, for lyso-Gb1 to be fully integrated into routine treatment decisions, further research is needed for “evaluating lyso-[Gb1] performance in predicting treatment status in larger, more diverse cohorts.”
