Researchers at Ben-Gurion University of the Negev and University of Colorado have created a dynamic new “smart” drug that is sensitive to the degree of inflammation, using a highly novel new approach.
The three describe a novel creative development of an anti-inflammatory engineered protein in the recent edition of the Journal of Immunology.
The uniqueness of this anti-inflammatory molecule can be found in a singular property; while it is injected as a non-active drug, excessive inflammation will activate it. Most other anti-inflammatory agents effectively inhibit inflammatory processes, but in a non-specific manner, and in areas that include sites of necessary normal inflammatory processes. The beauty of this invention lies in the use of a known natural biological code, says Dr. Peleg Rider, a researcher with the BGU Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences. “We mimicked a natural process that occurs during inflammation. The protein is actually a chimera comprised of two domains, both originating from the potent inflammatory cytokine family of IL-1.
“The first part of the protein holds the functional part of the molecule inactive, as occurs in normal living cells, and is connected to a potent natural inhibitor of IL-1.
“Upon encountering inflammatory enzymes, the molecule is cleaved and the functional part becomes active”, Rider explains.
The development is important since inhibition of inflammation in a non-specific manner reduces our natural ability to fight infections. This is a common side-effect of anti-inflammatory biologic therapeutics.
When a non-specific agent is used, any patient who suffers from local inflammation might then also be exposed to opportunistic infections at distant sites, such as lungs — risking, for example, tuberculosis.
This risk is mainly of concern to immuno-suppressed patients as well as older patients and patients undergoing chemotherapy as part of an anti-cancer treatment course, Rider said. He and BGU’s Dr. Eli Lewis and Prof. Charles Dinarello of the University of Colorado used a mouse model of local inflammation to demonstrate that leukocytes, which infiltrate inflammatory sites, indeed activate the chimeric protein, which in turn reduces local inflammation.
The activation of the protein correlated with the amount of inflammatory stimuli. Side effects are avoided because upon resolution of inflammation, the activation of the protein is also reduced.
The new chimeric molecule is protected by patent, owned by BGN Technologies, the technology transfer office of Ben-Gurion University and by the University of Colorado.
The research was supported by the Israeli Ministry of Economy’s Chief Scientist’s Office’s Kamin program.