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Biotech / Medical : Oxford GlycoSciences Plc -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (260)	12/15/2002 11:34:11 AM
From: tuck	Read Replies (1) \| Respond to of 469

Here's that NB-DNJ abstract: >>Published online before print December 11, 2002 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.262586099 Pharmacology Reversible infertility in male mice after oral administration of alkylated imino sugars: A nonhormonal approach to male contraception Aarnoud C. van der Spoel , Mylvaganam Jeyakumar , Terry D. Butters , Harry M. Charlton , Harry D. Moore , Raymond A. Dwek , and Frances M. Platt * *The Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom; and Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2UH, United Kingdom Edited by Ryuzo Yanagimachi, University of Hawaii, Honolulu, HI, and approved October 29, 2002 (received for review September 27, 2002) During mammalian spermatogenesis, male germ cells undergo a dramatic transformation, which includes a change of shape, nuclear condensation, and development of specialised structures, such as an acrosome, and a flagellum with a mitochondrial sheath. We have found a previously undescribed pharmacological approach to intervene in these events. After oral administration of the alkylated imino sugar N-butyldeoxynojirimycin (NB-DNJ) to mice, epididymal spermatozoa displayed a spectrum of abnormal head shapes, and acrosomal antigens were mostly absent or displayed irregular patterns. In addition, the mitochondria of these cells often had an aberrant morphology, and were arranged in relatively short and wide mitochondrial sheaths. The motility of the affected spermatozoa was severely impaired. After 3 weeks of administration of NB-DNJ, male mice became sterile, and regained their fertility during the fourth week off drug. The NB-DNJ-induced infertility was not associated with a reduction in the serum testosterone level. Biochemically, the capacity of imino sugars to impair spermatogenesis was associated with their potential to attenuate the biosynthesis of glucosylceramide-based sphingolipids. Our study reveals that male fertility is affected by partial glycosphingolipid depletion, or, alternatively, by a distinct as yet unidentified property that is shared by alkylated imino sugars that inhibit glucosylceramide biosynthesis. These compounds therefore may be new leads in the development of a male contraceptive, especially because NB-DNJ has already been through extensive evaluation in various mammals, including man. To whom correspondence should be addressed. E-mail: fran@glycob.ox.ac.uk.<< Full text would be nice, since they do not discuss the dosage in this abstract. I saw a paper that said the dose in the "seminal" trial for Gaucher's was 50mg three times daily, but that 100mg would be better. I think it was for six months. The study may predate the appearance of neurological effects. Anyone know or got a pointer to the dosage used for Gaucher's PIII? PS: the OGS web page is down. What's up with that? Cheers, Tuck