Using a non-invasive high-resolution imaging method, physicians found that long-term treatment with Cerezyme (imiglucerase) followed by a switch to Cerdelga (eliglustat) seemed to prevent or delay bone loss in a man with type 1 Gaucher disease.
The findings were described in a case report, “Impact on bone microarchitecture and failure load in a patient with type I Gaucher disease who switched from Imiglucerase to Eliglustat,” published in the journal Molecular Genetics and Metabolism Reports.
Gaucher disease is caused by a mutation in the GBA gene, which lowers the production of beta-glucocerebrosidase, an enzyme responsible for breaking down a fatty substance called glucocerebroside. As a result, glucocerebroside gradually builds up inside immune cells called macrophages, which then become Gaucher cells that infiltrate different organs and tissues.
Bone disease — resulting from the infiltration of Gaucher cells into the bone marrow — is one of the main manifestations of type 1 Gaucher disease, the most common form of the disorder. Bone weakening and increased vulnerability to fractures are frequent complications.
Although enzyme replacement therapy (ERT) and substrate reduction therapy (SRT), the most common treatments currently used to treat Gaucher, may ease some organ symptoms, their effects on the progression of bone disease are poorly understood. While ERT is designed to provide functioning beta-glucocerebrosidase, SRT lowers the production of glucocerebroside by partially blocking an enzyme called glucosylceramide synthase.
The limited understanding of bone disease in Gaucher is partly due to the lack of adequate methods to monitor changes in bone architecture and strength that can be used to estimate failure load, a parameter that reflects bone resistance to fractures.
In the case study, physicians described the first report of a patient with type 1 Gaucher in whom high-resolution peripheral quantitative computed tomography (HR-pQCT) — a novel non-invasive imaging method to analyze bone architecture and strength — was used to monitor the progression of bone disease.
The 39-year-old man was diagnosed with Gaucher at age 5 after complaining of bone pain that was not caused by bone disease and after completing a genetic test. At age 18, he started treatment with Cerezyme, an approved ERT marketed by Sanofi Genzyme, at a dose of 20 mg/kg, twice a month.
After a global shortage of Cerezyme caused treatment interruption at age 30, the patient switched to Cerdelga (84 mg twice daily), an approved SRT also marketed by Sanofi Genzyme, when he was 38.
HR-pQCT scans revealed that, for the most part, bone density and architecture tended to remain stable while the patient was on both treatments. Levels of white blood cells, platelets, and hemoglobin — the protein that carries oxygen in red blood cells — were also stable.
Using HR-pQCT coupled with mathematical analyses to calculate failure load, physicians discovered that failure load in the patient’s lower limbs improved over one year after he started Cerdelga. Steady improvements had already been seen with Cerezyme for three years.
“This is relevant because it showcases that treatment for the Gaucher disease, without the use of bone-modifying therapies … played an important role in combating the accelerated bone loss that was to occur from the [Gaucher disease] diagnosis in addition to age-related bone loss,” the researchers wrote.
They also said that future studies could use this new technology to assess approaches that impact bone quality in Gaucher patients.
Of note, one of the researchers has received speaker honorariums, travel grants, and consultation fees from Genzyme Corporation.
