Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5625_Библиотеки_им_академика_М_И_Перельмана

) is available from 2002, while no PC has reached the drug market yet, even though the IFG iminosugar reached Phase 2 of clinical trials. For this reason, many efforts have been devoted to identifying novel PCs for GD, by preparing multivalent compounds, introducing alkyl chains (both on sug­ars and iminosugars skeleton) to improve cellpermeability and by developing pH sensitive systems or noncompetitive inhibitors with the aim of favoring the enhancer activity with respect to the inhibitory one. In the last few years, the search for PCs for GD attracted even higher attention due to link between Gaucher and Parkinson disease, suggesting that effective PCs can be potentially applied to all protein misfolded diseases, including neurodegenerative disorders. DGJ ana­logs, IFG analogs, and aminocyclitols (e.g. valienamine derivatives) were investi­gated as PCs for GM1gangliosidosis and MBD, but all studies are at most at a preclinical level (mouse models). Regarding the glycogen storage disorder Pompe disease, the serious adverse effects caused in patients by coadministration of ERT with the natural iminosugar 1deoxynojirimycin (DNJ) stopped the ER/PC therapy clinical trial, despite the remarkable increase in enzyme activity observed. Lower side effects might be obtained with the Nbutyl enantiomer of the natural DNJ, which is a modest PC but does not act at all as enzyme inhibitor. The latter case suggests that noninhibitory chaperones, although more difficult to be identified, might represent a valuable alternative for a faster development of safe and efficient PCs for LSDs, in general.