Abstract
In cultivated Fibroblasts From late onset forms of MLD the degradation of the mutant enzyme is prevented in the presence of CBZ (Proc. Natl. Acad. Sci. USA 80, 6066, 83). - When CBZ (inhibitor of cathepsin B) was given i. v., i. p. or p. o. to female mice a time and dose dependent inhibition of the enzyme was demonstrated in the homogenates of different organs. Using 2 mg/kg i. v. (solvent: propanediol) the highest inhibition was found in the heart muscle (∼80 %) and the lowest in the brain (∼20 %). After 24 h the residual activity of the enzyme was 60 and 90 % of that of controls, suggesting de novo synthesis. Similar results were obtained by i. p. and p. a, administration of CDZ when 10 and 100 × higher doses were used (solvents: propanediol, DMSO). - Experiments with H3-CBZ revealed no correlation between accumulation of radioactivity and inhibition of cathepsin B in diFFerent organs. - Though CBZ permeates the blood-brain barrier it seems to be of no therapeutic benefit as it's solubility in organic solvents is low.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ullrich, K., Schmiereck, S. & Von Figura, K. 33 PROTEINASE INHIBITOR CBZ-PHE-ALA-CHN2 (CBZ): A DRUG FOR TREATMENT OF PATIENTS WITH METACRROMATIC LEUCO-DYSTROPHY (MLD)?. Pediatr Res 24, 266 (1988). https://doi.org/10.1203/00006450-198808000-00059
Issue Date:
DOI: https://doi.org/10.1203/00006450-198808000-00059