caa a22 4500 467932999 CHVBK 20180406152948.0 cr unu---uuuuu 170328e20060401xx s 000 0 eng 10.1007/s10545-006-0287-y doi (NATIONALLICENCE)springer-10.1007/s10545-006-0287-y Suzuki Yoshiyuki Clinical Research Center, International University of Health and Welfare, 2600-1 Kita-Kanemaru, 324-8501, Otawara, Japan aut β-Galactosidase deficiency: An approach to chaperone therapy [Elektronische Daten] [Yoshiyuki Suzuki] Summary: We propose a new molecular therapeutic approach to lysosomal diseases with severe neurological manifestations. Some low-molecular-weight compounds, acting as competitive inhibitors of a lysosomal enzyme in vitro, were found to stabilize and restore catalytic activities of the enzyme molecule as a molecular chaperone. We started this trial first in Fabry disease (generalized vasculopathy) using galactose and 1-deoxygalactonojirimycin, and then in β-galactosidase deficiency disorders (β-galactosidosis) with generalized neurosomatic and/or systemic skeletal manifestations (GM1-gangliosidosis and Morquio B disease), using a newly developed chemical compound N-octyl-4-epi-β-valienamine (NOEV). Administration of this chaperone compound resulted in elevation of intracellular enzyme activity in cultured fibroblasts from patients and genetically engineered model mice. In addition, substrate storage was improved after NOEV had been transported into the brain tissue via the blood-brain barrier. We hope this new approach (chemical chaperone therapy) will be useful for certain patients with β-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement. SSIEM and Springer, 2006 Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/2-3(2006-04-01), 471-476 0141-8955 29:2-3<471 2006 29 10545 https://doi.org/10.1007/s10545-006-0287-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0287-y text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Suzuki Yoshiyuki Clinical Research Center, International University of Health and Welfare, 2600-1 Kita-Kanemaru, 324-8501, Otawara, Japan aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/2-3(2006-04-01), 471-476 0141-8955 29:2-3<471 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer