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Biotech / Medical : Univec (UNVC)

UNVC 0.00270

+3.8%

Dec 24 9:33 AM EST

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To: Courtney Willfore who wrote (76)	11/5/1997 9:15:00 PM
From: r. peter Dale	Read Replies (1) of 181

Courtney - We may be online at the same time for once. That's excellent news for Univec - at a minimum it would be consistent with my understanding of the Company's favorable position v/v UNICEF. I would expect there will still be some delay in an announcement/ implementation since the Turner financing arrangements are so complex. I can only give a brief reply to your neurodegen. questions. Since you appear to be familiar with apoptosis, you probably know of the growing list of molecules associated with this phenomenon. So, in addition to bcl (bax, bad, bid, etc.), the TNF-related pathways, and the FAS/FasL involvement, there is the caspase family of proteases. Caspase-1 was previously known as interleukin-1 converting enzyme (ICE) and has a rich history in apoptosis. The caspases may prove to be a fertile area for pharmacological intervention of apoptosis: many caspases function by cleaving at highly specific 2-4 amino acid sequences in proteins and this cleavage is associated with apoptosis. Caspase inhibitors (which mimic the cleavage site and thus tie up the protease) are available and can significantly inhibit apoptosis. A recent report (Yakovlev et al., J. Neurosci. 17 [Oct. 1., 1997] 7415) showed that one of these inhibitors (DEVD) can effectively block caspase-3 *in vivo* and significantly reduced apoptosis in brain (in an animal model of traumatic brain injury). The animals also showed significantly improved neurological recovery. The key here is that the inhibitors are very small (~4 amino acids) and thus can easily reach the brain. There are lots of issues that need to be resolved here but at first glance this would meet some of your criteria as a potential pharmacological approach to thwarting those nasty macrophage. Do some research into caspases and the various DEVDs and report back. Peter

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