Thanks. For some reason, my first search in PubMed with N-butyldeoxygalactonojirimycin as the key word did not work. Now it does. I found the abstract you just posted, and some other stuff.
If I'm reading this one correctly, it means it shouldn't bother pregnant folks.
>>J Neurochem 1998 Feb;70(2):871-82
Inhibition of glycosphingolipid biosynthesis does not impair growth or morphogenesis of the postimplantation mouse embryo.
Brigande JV, Platt FM, Seyfried TN.
Department of Biology, Boston College, Chestnut Hill, Massachusetts 02167, USA.
Whole embryo culture (WEC) of organogenesis-stage mouse embryos was adapted for glycosphingolipid (GSL) metabolic studies to evaluate the hypothesis that de novo GSL biosynthesis is a prerequisite for growth and morphogenesis of the early postimplantation embryo. WEC supports the growth and development of postimplantation mouse embryos to stages that are indistinguishable from those achieved in vivo. N-Butyldeoxygalactonojirimycin (NB-DGJ) is an N-alkylated imino sugar that specifically inhibits biosynthesis of all glucosylceramide-based GSLs. NB-DGJ inhibited glucosylceramide and lactosylceramide biosynthesis nearly completely and inhibited ganglioside biosynthesis approximately 90% in both the embryo and visceral yolk sac. NB-DGJ also significantly reduced total ganglioside content in both the embryo and visceral yolk sac as estimated by the cholera toxin immunooverlay technique. A shift in expression from the structurally simple to the structurally complex gangliosides was also observed in NB-DGJ-treated embryos and yolk sacs. Despite causing major changes in GSL biosynthesis and composition, NB-DGJ had no effect on embryo viability, growth, or morphology. The findings suggest that de novo GSL biosynthesis may not be a prerequisite for the growth and morphogenesis of the organogenesis-stage mouse embryo.<<
The Zavesca insert says it is contra-indicated for pregnant ladies (or those considering getting pregnant), though I doubt many Gaucher's patients would become pregnant. It also mentions males (and females) should use birth control. Given that, I doubt this would be a huge issue with the FDA, either; just use the same warning. Further, from searching on the effects alpha-glucosidase inhibitors, it would appear that it's the alpha-glucosidase inhibition of Zavesca that causes the GI side effects. So even though, that's not mentioned in the OGT 923 abstract you posted (mouse farts hard to measure?), perhaps OGT 923 sidesteps those effects, as well.
Cheers, Tuck |
