Scientists have synthesized new molecules to treat autoimmune diseases
Last reviewed: 23.04.2024
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A team of scientists from the Weizmann Institute decided to challenge the autoimmune diseases. With diseases such as Crohn's disease and rheumatoid arthritis, the immune system mistakenly attacks the body's tissues. But scientists managed to deceive the immune system with an enzyme known as MMP9. The results of their research are published in the journal Nature Medicine.
Professor Irit Sagi and her research team have spent years searching for ways to block the action of the metalloproteinase enzyme (MMPs). These proteins are involved in the destruction of collagen, the main component of connective tissue. With autoimmune disorders, some fractions of these proteins, especially MMP9, are out of control, which leads to the progression of autoimmune diseases. Blocking these proteins can lead to the development of effective methods for treating autoimmune diseases.
Initially, Saga and her team developed synthetic molecules aimed directly at MMPs. But these drugs had very serious side effects. The body usually produces its own MMP inhibitors, known as TIMPs. Unlike synthetic drugs, they work very selectively. TIMP consists of a zinc ion, which is surrounded by three peptides of histidine, resembling a cork. Unfortunately, such molecules are rather difficult to reproduce in the laboratory.
Dr. Netta Sela-Pesswell decided to approach this problem from the other side. He did not develop a synthetic molecule to directly attack MMPs, but tried to stimulate the immune system through immunization. Just as immunization with killed viruses stimulates the immune system to create antibodies capable of attacking live viruses, immunization with MMPs would prompt the body to create antibodies that would block the enzyme in its active site.
Together with Professor Abraham Schoenzer, they created an artificial version of the zinc-histidine complex in the heart of the active MMP9 center. Then they introduced these small, synthetic molecules to mice, then checked the blood of mice for signs of immune activity against MMPs. The antibodies they discovered were called "metallobodies". They were similar but not identical, TIMPs, and a detailed analysis of their atomic structure showed that they work in a similar way - they block the active center of the enzyme.
With the introduction of metallobodies and the provocation of an inflammatory disease that mimicked Crohn's disease in mice, scientists found that the symptoms of autoimmune disease developed. "We are pleased not only with the tremendous potential of this method for the treatment of Crohn's disease," says Sagi, "but the possibilities of using this approach to study new treatments for many other diseases."
Now scientists from the Weizmann Institute have applied for a patent for synthetic immunization molecules, as well as generated metallobodies.
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