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Scientists have synthesized new molecules to treat autoimmune diseases
Last reviewed: 01.07.2025
A team of scientists from the Weizmann Institute of Science set out to challenge autoimmune diseases. In diseases such as Crohn's disease and rheumatoid arthritis, the immune system mistakenly attacks the body's tissues. But the scientists managed to trick the immune system with an enzyme known as MMP9. Their findings 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 enzyme metalloproteinases (MMPs). These proteins are involved in the breakdown of collagen, the main component of connective tissue. In autoimmune disorders, some fractions of these proteins, especially MMP9, go out of control, leading to the progression of autoimmune diseases. Blocking these proteins may lead to the development of effective treatments for autoimmune diseases.
Initially, Sagi and her team developed synthetic molecules that targeted MMPs directly. But these drugs had very severe side effects. The body normally produces its own MMP inhibitors, known as TIMPs. Unlike synthetic drugs, they work very selectively. A TIMP consists of a zinc ion surrounded by three histidine peptides, which resemble a cork. Unfortunately, such molecules are quite difficult to reproduce in the lab.
Dr. Netta Sela-Passwell decided to approach the problem from a different angle. Rather than designing a synthetic molecule to attack MMPs directly, he tried to stimulate the immune system through immunization. Just as immunization with killed viruses stimulates the immune system to create antibodies that can attack live viruses, immunization with MMPs would prompt the body to create antibodies that would block the enzyme at its active site.
Together with Professor Abraham Shanzer, they created an artificial version of the zinc-histidine complex at the heart of MMP9's active site. They then injected these small, synthetic molecules into mice, then tested the mice's blood for signs of immune activity against MMPs. The antibodies they found, called "metallobodies," were similar to, but not identical to, TIMPs, and detailed analysis of their atomic structure showed that they worked in a similar way - by blocking the enzyme's active site.
When they injected metallobodies and induced an inflammatory disorder that mimicked Crohn's in mice, the scientists found that symptoms of the autoimmune disease developed. "We're excited not only about the enormous potential of this approach for treating Crohn's," Sagi says, "but also about the potential for using this approach to explore new treatments for many other diseases."
Now scientists from the Weizmann Institute have applied for a patent on the synthetic immunization molecules, as well as the generated metallobodies.
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