molecular mechanism & effectiveness of an existing treatment for PBC

[Guest guest]

Scientists of the Center for Applied Medical Research

(CIMA) of the University of Navarra have discovered

the molecular mechanism responsible for the effectiveness of an existing

treatment for primary biliary cirrhosis, which combines two substances in order

to produce an effect that does not result from either substance separately……..

http://www.alphagalileo.org/index.cfm?_rss=1 & fuseaction=readrelease & releaseid=527475

Barb in Texas - Together in the Fight, Whatever it Takes!

Son Ken (33) UC 91 - PSC 99 - Tx 6/21 & 6/30/07 @ Baylor in Dallas

[Guest guest]

Well, that would seem to explain why corticosteroids works for PBC. The next

question (of course) is why it doesn't work for PSC. Interesting, and possibly

a research opportunity?

Arne

---- Barb Henshaw wrote:

=============

Scientists of the Center for Applied Medical Research (CIMA) of the

University of Navarra have discovered the molecular mechanism

responsible for the effectiveness of an existing treatment for primary

biliary cirrhosis, which combines two substances in order to produce an

effect that does not result from either substance separately....

[Guest guest]

Thanks for posting this news article Barb! For those interested in the original scientific paper, it's this one:

Arenas F, Hervias I, Uriz M, Joplin R, Prieto J, Medina JF 2008 Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest. 2008 Feb;118(2):695-709. PMID: 18188457.

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2176189 & blobtype=pdf

Another paper (by some of the same authors) was recently released in the "Articles in Press" section of Gastroenterology, showing that mice that are deficient in this chloride/bicarbonate anion exchanger (AE2) develop primary biliary cirrhosis-like disease with many of its hallmarks of human PBC .... including anti-mitochondrial antibodies, and T cell disturbances!

January T. Salas, Jesús M. Banales, Sarai Sarvide, Recalde, Ferrer, Iker Uriarte, P.J. Oude Elferink, Jesús Prieto, F. Medina. Ae2a,b-/- Deficient Mice Develop Antimitochondrial Antibodies and Other Features Resembling Primary Biliary Cirrhosis. Gastroenterology In Press Accepted Manuscript , Available online 18 February 2008 DOI: 10.1053/j.gastro.2008.02.020

It's further interesting that the AE2 protein is probably acting in concert with the cystic fibrosis protein (a chloride channel) to facilitate bicabonate enrichment of bile. So the cystic fibrosis gene (CFTR) is implicated in PSC, and now the AE2 protein with PBC. Fascinating!

Dave

(father of (22), PSC 07/03; UC 08/03)