According to the report of the American Physicists Organization Network on December 26 (Beijing time), recently, the Weizmann Institute of Science in Israel changed its previous treatment strategy, using artificial molecules to induce the immune system to produce special antibodies that can block itself MMP9, an enzyme that plays an important role in immune diseases, has achieved success in animal experiments. The newly synthesized molecules have great potential in the treatment of immune system diseases such as Crohn's disease, and open up new directions for the search for the treatment of immune diseases. Related papers were published on the website of the journal Nature.
MMP is a family of matrix metalloproteinases and plays a key role in cell mobilization, division, wound healing, etc. If some of them, especially MMP9, get out of control, it will cause autoimmune diseases and cancer metastasis. Blocking these proteins is expected to find a cure for autoimmune diseases. In the beginning, the researchers designed an artificial drug molecule that directly aimed at all MMP members, but it was too rough and had great side effects.
Professor Eliot Saki of the Institute of Bioregulation explained that under normal circumstances, the body can also produce its own MMP inhibitor, called TIMP, as a deflation procedure to control MMP enzymes. These naturally-produced TIMPs are highly selective and consist of three histidine peptides surrounding a metal zinc ion. Each arm is extremely precise and just reaches the groove of the active site of the MMP enzyme, blocking it like a cork. The groove makes the MMP inactive. "It is very difficult to replicate this accuracy."
The researchers turned to other alternatives instead of designing a molecule, but attacking MMP directly. Just as dead viruses trigger the immune system to produce antibodies and attack live viruses, they came up with a way to "trick" the body through the MMP immune response to generate natural antibodies that target MMP9 and lock its active site.
They artificially synthesized a metal zinc-histidine complex at the core active site of MMP9, and then injected these small molecules into mice, and examined the immune response signals of MMP enzymes in the blood of mice. The researchers conducted a detailed analysis of the atomic structure of the antibody produced, and found that it is different from TIMP, but the effect is very similar, it can also reach the groove of the enzyme and block the active site. Antibodies can selectively target only two members of the MMP family, MMP2 and MMP9, and bind them tightly.
In order to test the efficacy, they simulated Crohn's disease in mice to cause inflammation, and then injected the antibodies produced by the above metal zinc-histidine complex for treatment, and found that the symptoms disappeared. The Weedman Institute Yeda Technology Transfer Company has applied for a patent for this synthetic immune molecule and its antibodies.
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