Biochemical evaluation of intracerebroventricular rhNAGLU-IGF2 enzyme replacement therapy in neonatal mice with Sanfilippo B syndrome

التفاصيل البيبلوغرافية
العنوان: Biochemical evaluation of intracerebroventricular rhNAGLU-IGF2 enzyme replacement therapy in neonatal mice with Sanfilippo B syndrome
المؤلفون: Brett E. Crawford, Mark S. Sands, Ibrahim Elsharkawi, Steven Q. Le, Patricia I. Dickson, Jonathan D. Cooper, Linley Mangini, Roger Lawrence, Shih-hsin Kan, Heather Prill
المصدر: Mol Genet Metab
بيانات النشر: Elsevier BV, 2021.
سنة النشر: 2021
مصطلحات موضوعية: 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Recombinant Fusion Proteins, Endocrinology, Diabetes and Metabolism, Mucopolysaccharidosis, 030105 genetics & heredity, Biochemistry, Article, Mice, Mucopolysaccharidosis III, 03 medical and health sciences, chemistry.chemical_compound, Dogs, 0302 clinical medicine, Endocrinology, Insulin-Like Growth Factor II, Internal medicine, Acetylglucosaminidase, Genetics, Animals, Humans, Medicine, Enzyme Replacement Therapy, Dosing, Molecular Biology, Sanfilippo syndrome, Mice, Knockout, business.industry, Therapeutic effect, nutritional and metabolic diseases, Heparan sulfate, Enzyme replacement therapy, medicine.disease, Fusion protein, Disease Models, Animal, Infusions, Intraventricular, Animals, Newborn, chemistry, Sanfilippo B syndrome, Heparitin Sulfate, Nervous System Diseases, business, 030217 neurology & neurosurgery
الوصف: Mucopolysaccharidosis IIIB (MPS IIIB, Sanfilippo syndrome type B) is caused by a deficiency in α-N-acetylglucosaminidase (NAGLU) activity, which leads to the accumulation of heparan sulfate (HS). MPS IIIB causes progressive neurological decline, with affected patients having an expected lifespan of approximately 20 years. No effective treatment is available. Recent preclinical studies have shown that intracerebroventricular (ICV) ERT with a fusion protein of rhNAGLU-IGF2 is a feasible treatment for MPS IIIB in both canine and mouse models. In this study, we evaluated the biochemical efficacy of a single dose of rhNAGLU-IGF2 via ICV-ERT in brain and liver tissue from Naglu(−/−) neonatal mice. Twelve weeks after treatment, NAGLU activity levels in brain were 0.75-fold those of controls. HS and β-hexosaminidase activity, which are elevated in MPS IIIB, decreased to normal levels. This effect persisted for at least 4 weeks after treatment. Elevated NAGLU and reduced β-hexosaminidase activity levels were detected in liver; these effects persisted for up to 4 weeks after treatment. The overall therapeutic effects of single dose ICV-ERT with rhNAGLU-IGF2 in Naglu(−/−) neonatal mice were long-lasting. These results suggest a potential benefit of early treatment, followed by less-frequent ICV-ERT dosing, in patients diagnosed with MPS IIIB.
تدمد: 1096-7192
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::236cda32bdff62621fb55d1bf4f55e9b
https://doi.org/10.1016/j.ymgme.2021.03.013
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....236cda32bdff62621fb55d1bf4f55e9b
قاعدة البيانات: OpenAIRE