New synthetic molecules treat autoimmune disease in mice

Weizmann Institute of Science ^ | December 25, 2011

[decimon]

A team of Weizmann Institute scientists has turned the tables on an autoimmune disease. In such diseases, including Crohn's and rheumatoid arthritis, the immune system mistakenly attacks the body's tissues. But the scientists managed to trick the immune systems of mice into targeting one of the body's players in autoimmune processes, an enzyme known as MMP9. The results of their research appear today in Nature Medicine.

Prof. Irit Sagi of the Biological Regulation Department and her research group have spent years looking for ways to home in on and block members of the matrix metalloproteinase (MMP) enzyme family. These proteins cut through such support materials in our bodies as collagen, which makes them crucial for cellular mobilization, proliferation and wound healing, among other things. But when some members of the family, especially MMP9, get out of control, they can aid and abet autoimmune disease and cancer metastasis. Blocking these proteins might lead to effective treatments for a number of diseases.

Originally, Sagi and others had designed synthetic drug molecules to directly target MMPs. But these drugs proved to be fairly crude tools that had extremely severe side effects. The body normally produces its own MMP inhibitors, known as TIMPs, as part of the tight regulation program that keeps these enzymes in line. As opposed to the synthetic drugs, these work in a highly selective manner. An arm on each TIMP is precisely constructed to reach into a cleft in the enzyme that shelters the active bit – a metal zinc ion surrounded by three histidine peptides – closing it off like a snug cork. 'Unfortunately,' says Sagi, 'it is quite difficult to reproduce this precision synthetically.'

[Smokin' Joe]

Ping! (Thanks, decimon!)

[Smokin' Joe]

Ping! (Thanks, decimon!)

[MinorityRepublican]

I was diagnosed with Crohn’s Disease back in ‘04 and like you I was suffering until Remicade literally cured me. Also, I’ve heard others use Humira and that drug works great too. However, I know both drugs are not for everyone but have you tried one of them?

[Smokin' Joe]

Thank you for the ping, neverdem!

[yefragetuwrabrumuy]

Just some FYI articles you might find interesting.

http://www.eurekalert.org/pub_releases/2011-01/nu-npc012611.php

http://www.webmd.com/ibd-crohns-disease/crohns-disease/news/20040519/wormy-cocktail-fights-crohns-disease

[afnamvet]

Thanks for the ping neverdem. I jusy passed the 38 year mark with Crohn’s. Nine major surgeries and now doing OK on Remecade.

[Gene Eric]

Awesome news.

I became familiar with this complicated topic years ago, fortunately for unrelated reasons. It’s a scary enmeshed state for the immune system to be in.