Biochemical response to substrate reduction therapy versus enzyme replacement therapy in Gaucher disease type 1 patients
| العنوان: | Biochemical response to substrate reduction therapy versus enzyme replacement therapy in Gaucher disease type 1 patients |
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| المؤلفون: | Carla E. M. Hollak, Mina Mirzaian, Patrick Wisse, Maria J. Ferraz, Herman S. Overkleeft, Johannes M. F. G. Aerts, Bouwien E. Smid, Marri Verhoek |
| المساهمون: | Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Graduate School, Other departments, Medical Biochemistry, Amsterdam Cardiovascular Sciences |
| المصدر: | Orphanet Journal of Rare Diseases Orphanet journal of rare diseases, 11(1). BioMed Central Orphanet Journal of Rare Diseases, 11, 28 |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, 1-Deoxynojirimycin, Pyrrolidines, Disease, Glucosylceramides, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Miglustat, medicine, Humans, Genetics(clinical), Pharmacology (medical), Substrate reduction therapy, Enzyme Inhibitors, Genetics (clinical), Eliglustat, Chitotriosidase, Medicine(all), Gaucher Disease, business.industry, Research, CCL18, nutritional and metabolic diseases, General Medicine, Enzyme replacement therapy, Blood proteins, Glucosylceramidase, 030104 developmental biology, Endocrinology, 030220 oncology & carcinogenesis, Glucosylsphingosine, Glucosylceramide, Female, business, medicine.drug |
| الوصف: | Background We retrospectively compared biochemical responses in type 1 Gaucher disease patients to treatment with glycosphingolipid synthesis inhibitors miglustat and eliglustat and ERT. Methods Seventeen GD1 patients were included (n = 6 eliglustat, (two switched from ERT), n = 9 miglustat (seven switchers), n = 4 ERT (median dose 60U/kg/m). Plasma protein markers reflecting disease burden (chitotriosidase, CCL18) and lipids reflecting substrate accumulation (glucosylsphingosine, glucosylceramide) were determined. Also, liver and spleen volumes, hemoglobin, platelets, and fat fraction were measured. Results In patients naïve to treatment, chitotriosidase, CCL18 and glucosylsphingosine decreased comparably upon eliglustat and ERT treatment, while the response to miglustat was less. After 2 years, median decrease of chitotriosidase was 89 % (range 77–98), 88 % (78–92) and 37 % (29–46) for eliglustat, ERT and miglustat naïve patients respectively; decrease of CCL18 was 73 % (63–78), 54 % (43–86), and 10 % (3–18); decrease of glucosylsphingosine was 86 % (78–93), 78 % (65–91), 48 % (46–50). Plasma glucosylceramide in eliglustat treated patients (n = 4) reached values below the normal range (n = 20 healthy controls). Biochemical markers decreased or stabilized in switchers from ERT to eliglustat (n = 2), but less in miglustat switchers (n = 7). Clinical parameters responded comparably upon eliglustat and ERT treatment. Conclusions Our explorative study provides evidence that biochemical markers respond comparably in patients receiving eliglustat treatment and ERT, while the corresponding response to miglustat treatment is less. |
| اللغة: | English |
| تدمد: | 1750-1172 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4346b8d3c90c6f1429341c58c8d6fce1Test https://doi.org/10.1186/s13023-016-0413-3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4346b8d3c90c6f1429341c58c8d6fce1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17501172 |
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