I get email.
:-)
When I said that antegren isn't a "gimme", I didn't mean that I'm not excited about its potential.
There are intense efforts to make small molecule inhibitors of alpha4beta1 and alpha4beta7 interactions with their ligands. Biogen itself has an advanced program. Merck has been publishing on their efforts for ages. Genentech is interested and has had successes, at least at the peptide level (long ago).
Alpha4 integrin is a validated target. Everybody and their brother would like to be in the position that the Biogen/Elan collaboration is in. But neither Crohn's nor MS are no-brainers. The projects are high risk, and everybody at both companies will be sweating it when the final data rolls in from the four phase III trials.
Here's the latest abstract to show in medline. Don't know why it's late, but it was just posted. Don't know whose molecule CT301 is, and there's plenty of reason to wonder if EAE is in fact a decent model of MS........
J Neuroimmunol 2002 Oct;131(1-2):147-59
Prolonged reversal of chronic experimental allergic encephalomyelitis using a small molecule inhibitor of alpha4 integrin.
Piraino PS, Yednock TA, Freedman SB, Messersmith EK, Pleiss MA, Vandevert C, Thorsett ED, Karlik SJ.
Department of Physiology, London Health Sciences Center, University of Western Ontario, N6A 5C1, London, ON, Canada
CNS leukocytic invasion in experimental allergic encephalomyelitis (EAE) depends on alpha4beta1 integrin/vascular cell adhesion molecule-1 (VCAM-1) interactions. A small molecule inhibitor of alpha4beta1 integrin (CT301) was administered to guinea pigs in the chronic phase (>d40) of EAE for 10, 20, 30 or 40 days. CT301 elicited a rapid, significant improvement in the clinical and pathological scores that was maintained throughout the treatment period. A progressive loss of cells in the spinal cord of treated animals confirmed the resolution of inflammation associated with clinical recovery. Therefore, prolonged inhibition of alpha4beta1 integrin caused a sustained reversal of disease pathology in chronic EAE and may be similarly useful in MS. |
